Evidence indicates that clozapine is effective in the management of treatment-resistant schizophrenia and in affective psychoses. To examine whether affective components within the boundaries of the schizophrenia spectrum imply specific psychopathological characteristics of response to treatment, 60 patients with a treatment-resistant schizophrenia spectrum disorder who were treated with clozapine (75-600 mg/d) were evaluated in a naturalistic, open, follow-up study. The group comprised 41 patients with and 19 without bipolar features (43 men and 17 women, mean age 34.3 years). Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS) during the first year of treatment. The results show a significant improvement in scores in both groups (P < 0.001) compared with the baseline evaluation. A higher percentage of responders was seen in the 'affective' group. No typical psychopathological characteristic or symptom cluster predicting the response to treatment was identified. During the study, 15 patients discontinued treatment: six for lack of efficacy, five for non-compliance and four for adverse events. The study confirms the efficacy of clozapine in the treatment of schizophrenia spectrum disorders, particularly in patients with bipolar features.