A 3-year open-label study was conducted to determine the long-term safety and efficacy of quetiapine monotherapy in schizophrenia and schizoaffective disorder.Twenty-three male outpatients previously stable but with inter-episode residual symptoms on classical antipsychotics and/or risperidone and who had complained of side effects were selected. To initiate quetiapine, patients were hospitalized for 13 days and then treated as outpatients. Quetiapine dosage was adjusted according to therapeutic effects. Only five patients (21.7%) completed 77 to 96 weeks of the study. Initial dose was 261 +/- 65.6 mg/day (mean +/- S.D.) administered in divided doses, with an ending dose of 487 +/- 209.6 mg/day, corresponding with an 86.6% dose increase over the course of the study. For those completing 12 weeks or less (n = 11), mean ending dose was 362 +/- 184.8 mg/day a 38.7% dose increase over baseline. For those completing 25 weeks or more (n = 12), mean ending dose was 592 +/- 178.2 mg/day, a 126.8% dose increase over baseline. Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met criteria for supersensitivity psychosis (SSP).Therapeutic tolerance and rebound psychosis were found to develop with quetiapine in male patients with a history of chronic treatment with classical antipsychotics. Seeman and Tallerico3 have proposed pharmacologic explanations for quetiapine and clozapine drug-induced rebound phenomena.