Since most clinical trials of atypical antipsychotics have been conducted in hospitalized patients, a Phase-IV, multicentre, 8-week, open-label, flexible-dose study was performed to assess the efficacy and safety of risperidone in outpatients with schizophrenia. Three hundred and thirty patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) diagnosis of schizophrenia were enrolled at 61 Canadian sites. Upon trial entry, the patients had their neuroleptic and antiparkinsonian drugs discontinued, and treatment with risperidone was initiated at a dose of 2 mg daily, then increased by 2 mg daily on each of the 2 following days until the initial target dose of 6 mg daily was reached on day 3. No further titration was allowed until day 14, after which the dose could be increased or decreased. During the stabilization phase (days 14-56), the dose was unchanged in 44% of the patients, increased in 24%, decreased in 23%, and titrated both up and down in 9% of the patients. In the efficacy-evaluable population (n = 292), treatment with risperidone produced substantial (-26.4) and significant (P = 0.0001) improvement in the total Positive and Negative Syndrome Scale (PANSS) score. At the end of the study (week 8), 85% of patients were classified as clinically improved according to an a priori definition (that is, 20% or more decrease from baseline in total PANSS score). On their last study visit, 75% of patients reported their experience with risperidone as better than their previous neuroleptic therapy. Risperidone was generally well tolerated. The adverse events reported by more than 5% of the patients were insomnia, nausea, headache, somnolence, dizziness, fatigue, anxiety, vomiting, and ejaculation disorder. Seventy-four percent of the reported treatment-related adverse events were recorded during the first 2 weeks of the trial, possibly because of the discontinuation of prior neuroleptic and antiparkinsonian drugs followed by immediate upward titration of risperidone. However, only 8.5% of adverse events were reported to have occurred during week 3, and only 0.8% of adverse events were reported for week 8. Risperidone treatment produced significant improvements over baseline in the incidence and severity of extrapyramidal symptoms (EPS). A slight but statistically significant increase in body weight was observed. The results of this open-label, Phase-IV trial in a large population of outpatients with schizophrenia found that risperidone was superior to the neuroleptics that patients had previously taken in terms of efficacy and severity of EPS. Our results suggest the use of risperidone at lower doses in outpatients with schizophrenia.