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In the powerful drama Deep End of the Ocean, which opens Friday, Pfeiffer plays Beth Cappadora, a devoted wife and mother whose middle child is kidnapped.
After the boy is abducted, Beth barely copes.
Nine years later, the child is found and returned to the family but this miracle has its downside because the boy has bonded with another family.
"I couldn't sit through Mel Gibson's Ransom because it was about a kidnapping," Pfeiffer recalls. "I bolted from the theatre after about 30 minutes because I found the whole idea of losing a child much too harrowing."
Yet Pfeiffer tenaciously sought the film rights to Jacquelyn Mitchard's best-selling 1996 novel about a kidnapping and was determined to play Beth.
"I don't think I could, or would have even read the novel if I didn't know that the boy was eventually found. That first third of the novel was still very heart-wrenching.
"This is every mother's worst nightmare.
"As I was reading, I asked myself if I could ever get through something like this and that's as far as I got.
"You simply don't venture further. It's way, way beyond what you even want to contemplate."
Once she had secured the film rights to The Deep End of the Ocean, Pfeiffer had to take that next step and contemplate what kind of effect a kidnapping would have on a mother.
"It was one of the most unpleasant things I had to do -- even if it was just hypothetical. I had to probe my soul as to why I even wanted to subject myself to this kind of emotional torture."
The answer was the reason Pfeiffer wanted to do the movie in the first place.
"Jacquelyn's story is not about a kidnapping. It's about what a family really is, and redefining marriage. There are many different kinds of families beyond the simple biological one.
"There are adopted families and many kinds of extended families."
Pfeiffer was not in a relationship in 1993 when she applied to adopt a child.
The previous year, she had broken off her three-year relationship with actor Fisher Stevens when rumours surfaced that he was cheating on her.
It was the latest in a string of failed relationships.
She was married briefly to Thirtysomething star Peter Horton whom she'd met in an acting class, and dated Michael Keaton long before she played Catwoman to his Batman.
During the filming of Dangerous Liaisons, she had an affair with her married co-star John Malkovich.
"When I decided to adopt a child, I believed I was going to be a single parent, but that's not how it worked out," says Pfeiffer.
Two weeks after she had made her adoption application, friends set Pfeiffer up on a blind date with David E. Kelley, the creator of such TV shows as Picket Fences, Chicago Hope, The Practice and Ally McBeal.
"Our family all happened at once. David and I fell in love and he was eager to become Claudia Rose's father."
Claudia Rose arrived in Pfeiffer and Kelley's lives in March 1993. They were married the following November and their biological son John Henry Kelley was born the following August.
"This makes our family pretty conventional compared to what Jacquelyn is dealing with in The Deep End of the Ocean."
Pfeiffer has learned to juggle her family and career, always placing her children above her films.
"I take the children with me to the set and I won't do projects that would take me away from Los Angeles for an extended period of time. I want my children to have as normal a childhood as possible."
True to her word, Pfeiffer turned down Disney's offer to star in Evita because she would have had to film in Europe and Argentina.
She has just signed to star opposite Harrison Ford in the science fiction romance What Lies Beneath.
"It's a ghost story about a man who goes back in time to find the woman he loved. It's a great romantic notion, and I've never worked with Harrison. He's one of the best, so I jumped at the chance."
Pfeiffer was recently voted 'the star who matters the most to box-office."
"It dumbfounded me. I'm certainly not the highest-paid actress in the industry. That's for sure.
"I think it means that I'm the actress whose movies never make any money, but I still keep getting hired. Whatever logic they used, I'm flattered."
Most of her emotional work for Deep End of the Ocean was pure acting, but she did have one real moment to draw on.
"I always check on the kids a couple of times each night after they go to bed.
"This one night, the first time I checked, they were both sleeping peacefully. An hour later, I checked again and Claudia Rose was not in her bed.
"I panicked and woke David up. He watched as I frantically checked our bed all the time knowing she was asleep under our huge fluffy comforter.
"It was a moment of pure terror that I've never experienced before or since. I chided David for not telling me instantly he knew where she was."
Pfeiffer recalls that when she was 5, she ran away from home.
"My parents were playing cards with some friends and I felt they were ignoring me, so I snuck over to a neighbor's house and asked them to hide me. They probably told my parents, but in any case I didn't get scolded because they were so glad to see me.
"I ran away again when I was 16, but that was a whole different story. I was a bit of a handful back then. I guess that's something I have to look forward to as a parent."
THE PFEIFER FILE
HOLLYWOOD -- Michelle Pfeiffer admits it feels like a million lifetimes ago that she was working at the checkout counter of a grocery store in Southern California.
"I'd stare at the magazines dreaming that one day I could be an actress too," recalls Pfeiffer.
One day, she handed in her uniform, entered a beauty contest, got herself an agent and enrolled in acting classes.
Her first job was on TV's Fantasy Island. She had one line but the exposure got her a string of commercials and a string of bit parts on TV shows including Delta House and The Solitary Man.
Pfeiffer says if she were to choose the highlights of her career to date, they probably wouldn't mirror those a film historian might select.
* 1981 The Children Nobody Wanted:
"For me, this is the first real milestone in my career. It wasn't just my first lead in a TV movie but the producers wanted me for my acting not my looks.
"Every other job I'd got was predicated on how I looked. This one, they wanted me not to wear makeup and to look as bad as I could."
* 1982 Grease 2:
"For better or for worse, Grease 2 gave me real exposure. For a brief moment, audiences, directors and producers did a double take."
* 1983 Scarface:
"I learned I got the role because (director) Brian DePalma wanted an unknown to play Al Pacino's wife. I don't really care why I got the role, I'm just grateful that so early in my career I got to work with one of the most respected actors of our generation.
"I learned so much from watching him work."
(Pfeiffer was reunited with Pacino in 1991 in the romantic comedy Frankie & Johnny).
* 1987 The Witches of Eastwick:
"This was the first movie I was in that made real money. It was kind of thrilling to be in a genuine box-office hit.
"I learned how much clout that gives you as an actor even if it's only fleeting."
(Pfeiffer worked with Jack Nicholson in Witches. He asked her to be his co-star for Wolf in 1994).
* 1988 Dangerous Liaisons:
"This was my first Oscar nomination. It was a validation from my peers. You don't work for awards or even award nominations but they are a nice byproduct."
(Pfeiffer was nominated again the following year for The Fabulous Baker Boys and again in 1993 for Love Field.)
* 1994 Dangerous Minds:
"This was the first movie that I actually felt I carried and it was so rewarding that it was a hit."
(After the success of Dangerous Minds, Pfeiffer became one of Hollywood's higher paid actresses. She commands upwards of $5 million US a picture.)
* 1997 A Thousand Acres:
"This was a film Jessica Lange and I literally had to fight to get made. It may not have been a commercial success but it was a personal success for me as a producer because I got it done against incredible odds."
(Pfeiffer's company Via Rose also produced or co-produced Love Field, Dangerous Minds, One Fine Day and The Deep End of the Ocean.)