Clozapine has been increasingly shown to be effective in the acute and maintenance treatment of bipolar disorders. For this reason, we studied whether clozapine alone is effective as a mood stabilizer in patients with refractory bipolar disorders.Subjects were part of a long-term follow-up study cohort of 193 patients with refractory mood disorders who were treated with clozapine at McLean Hospital prior to July 1, 1992. Patients included in this study were those older than 16 years with bipolar disorder (manic or mixed) and schizoaffective disorder, bipolar type, discharged taking clozapine alone (N = 17). Hospital records on all patients were reviewed by trained raters blind to "best-estimate" diagnoses. Response to clozapine was determined by the Clinical Global Impressions-Improvement (CGI-I) scale. Patients were contacted at least 6 months after clozapine initiation for semistructured follow-up interviews by raters blind to diagnosis and baseline information.Seventeen subjects were contacted 16.1 +/- 5.6 months after clozapine initiation. Most of the 17 patients had previously failed trials of lithium, valproate, carbamazepine, neuroleptics, combinations of these, and electroconvulsive therapy; or had tardive dyskinesia. Of these patients, 65% (11/17) continued to be on clozapine therapy alone at follow-up and had no subsequent rehospitalization or affective episode. At follow-up, there was a significant decrease in the rehospitalization rate (p = .025) than before starting clozapine and a significant improvement in CGI-I scores (p = .02).Clozapine monotherapy is an effective mood stabilizer, reducing both the number of affective episodes and rehospitalizations in patients with severe refractory bipolar illness.