Some bipolar patients with acute manic episodes can be refractory to conventional treatment with mood stabilizers. Clozapine, an atypical antipsychotic, has been reported to be effective in adults with treatment-resistant bipolar disorder. We describe the therapeutic effect of clozapine in 10 adolescent inpatients (12- to 17-year-olds) with severe acute manic or mixed episodes who did not improve after treatment with conventional drugs (mood stabilizers, antipsychotics). At hospital discharge, 15 to 28 days after clozapine treatment, all patients had responded positively according to the Clinical Global Impression-Improvement Scale scores. The mean changes in Mania Rating Scale, Brief Psychiatric Rating Scale, Children's Global Assessment Scale, and Clinical Global Impression-Severity Scale were significant (p < 0.001). Clozapine dosage was 142.5 ± 73.6 mg/day (range 75-300 mg/day). Side effects (increased appetite, sedation, enuresis, sialorrhea) were frequent but not severe enough to require reduction of dosage. Mean weight gain after 6 months was 6.96 ± 3.08 kg (10.7%). Neither decrease of white cells nor epileptic seizures were reported during follow-up (12-24 months). These preliminary findings suggest that clozapine may improve the clinical picture in adolescents with treatment-refractory manic or mixed episodes. Controlled studies on larger samples are warranted.