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Cruella De Vil (Glenn Close) is the main antagonist of 101 Dalmatians and 102 Dalmatians. The character originally appeared in a 1961 animated film.

The film reinvented Cruella as the vindictive, snobbish, and glamorous magnate of a haute couturefashion house, "House of DeVil", which specialised in fur couture. However she is still rude, arrogant and short-tempered like her 1961 animated counterpart. The character of Anita (played by Joely Richardson) was a couturière and employee of De Vil. Unlike the animated film, the live-action version gives the reason why Cruella wanted to make the puppies into coats at a young age, is that their fur wouldn't be as soft when they fully grow up. At the start of the film, it is revealed that Cruella has secretly had her henchmen slaughter a white Siberian tiger at London Zoo for its pelt. However, the suspicions and accusations of the Dearly family force Cruella to step up her plans to make the puppies into a coat, the puppies escaping while her henchmen are preparing to do the work and Cruella being subsequently thrown into a vat of molasses and a pig pen when she tries to track them to a farm. At the end of the film, she is arrested and sent to prison, with her business going downhill. Anita's husband Roger then creates a video game with her as the villain which becomes very popular.

This film increased the physical comedy of the animated film, even veering into more juvenile humor, such as Cruella falling into a vat of old molasses. Close's performance was universally well-received and her sex appeal as the character was also credited.

The live-action film was not as critically successful as the animated movie, but Close's performance, as well as her costumes, by Anthony Powell and Rosemary Burrows, received appreciative attention, including a spread in Vanity Fair. Claws were applied to gloves, and necklaces were made from teeth, to add to the idea that Cruella enjoyed wearing parts of dead animals. Nails were also projected from the heels to make them especially vicious in appearance. Some of her clothes were made out of leather or PVC, and Cruella always wore lots of makeup. Close has commented on how demanding the slapstick physicality of the role was while wearing nail-heeled boots and corsets. She was always smoking to give the appearance of a mysterious "villain". Close also insisted that she fall into the molasses herself for genuine acting, as opposed to delegating it to a stunt double.

In 102 Dalmatians, while under effect of Dr. Ivan Pavlov's hypnotherapy treatment, Cruella was cured of her fur addiction and released from prison on parole, three years after the events of the first film. She insisted on being called "Ella" because "Cruella sounds so... cruel". Reformed, completely devoted to saving animals, and while experiencing "doraphobia", she was scared by even the smallest sight of fur fashion, especially since she had all of her fur clothing and the drawing of herself in a Dalmatian puppy coat boarded up. Unfortunately, this new persona was not to last for long since the effects of Big Ben's chimes managed to undo the conditioning, reverting Cruella to her former self. During the "Ella" stage, Cruella quit her characteristic habits, such as wearing fur clothing, long nails, extravagant hair styles, and of course, smoking. Once Big Ben jolted her brain waves back into Cruella, her old habits returned, with Cruella redesigning the sketch of the original Dalmatian coat to include a hood specifically so that she can use three new puppies to make the coat on top of the original ninety-nine puppies required, the chosen extra three being the children of Dipstick, one of the Dearlys' original fifteen puppies. However, despite her efforts to distract attention from herself by framing the owner of the Second Chance Dog Shelter for her crimes (the only person who stands to benefit if she reverts to her old behavior as her parole states that her fortune will go to dog shelters in the Westminster area and Second Chance is the only such shelter), her plans are discovered by her parole officer, also Dipstick's owner. Her accomplice, furrier Jean Pierre Le Pelt, is trapped in one of his own coats when it is sown shut during a fight in an illegal sweatshop in France, while Dipstick's daughter Oddball (who has yet to develop her own spots) lures Cruella into a trap where she is literally baked into a massive cake and arrested along with Le Pelt, both being sentenced to life in prison for their actions.

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