Sir Anthony Hopkins was reportedly furious and heartbroken when Jodie Foster decided that she wasn't going to return in the role of Clarice Starling; he was also disappointed that Jonathan Demme would not return to direct.
Sir Anthony Hopkins wrote a screenplay for a sequel to this movie, most likely titled "Hannibal Ending", which would've involved Starling killing Lecter. However, this was never used.
(at around 34 mins) When Dr. Hannibal Lecter (Sir Anthony Hopkins) is seen in his study playing the piano, on the desk to the right of the frame a book can be seen open displaying the painting of the Red Dragon.
The part of Mason Verger was originally offered to Christopher Reeve, based on his work as a wheelchair-bound police officer in Above Suspicion (1995), which was released six days before the horse riding accident that left Reeve paralyzed for real. Not having read the novel, Reeve showed initial interest in the role, but ultimately declined upon realizing that Verger was a quadriplegic, facially-disfigured child rapist.
After years of being actively involved in getting this sequel made during no less than fifteen drafts of the screenplay, Jodie Foster ultimately declined to participate in the sequel. She issued a statement at the time (clearly to no benefit of this movie) saying "I had been offered more money than ever in my entire career to make this film. But who cares if it betrays Clarice, who has become like a person to me, in the end." Ironically, Foster had to fight tooth and nail for years to land the role of Clarice in The Silence of the Lambs (1991).