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A high point in Hoskins's career was portraying the private investigator Edward "Eddie" Valiant in the live-action/animated family blockbuster Who Framed Roger Rabbit (1988). Hoskins was not the first choice for the role – Harrison Ford, Bill Murray and Eddie Murphy were all considered for the part.[24] Film critics, among them Gene Siskel and Roger Ebert, agreed that Hoskins was perfect for the role.[25] As his character interacts and makes physical contact with animated characters in the film, Hoskins was required to take mime training courses in preparation. He experienced hallucinations for months after production on the film had ended.[26] He was nominated for a Golden Globe Award and won a British Evening Standard Award for his performance.
A2012 article by Express quotes Hoskins as saying, "I had trained myself to hallucinate, and in the end, it screwed up my brain." He also admitted that after filming had wrapped, he would"be sitting, talking normally and suddenly a weasel would creep out of the wall at me." He noted that while his doctors encouraged him to take a bit of time off to decompress from the stress of being in such a big, odd movie, Hoskins went a bit further than theirrecommendation of a five-month sabbatical, taking a full year off after "Who Framed Roger Rabbit" became a massive success upon its release in the summer of 1988.