A 15 year-old adolescent boy with a severe treatment refractory bipolar disorder type I, most recent episode manic, severe with psychotic features had previously required hospitalizations and treatment with lithium and/or carbamazepine and high doses of standard neuroleptics without any response. A treatment with a combined clozapine-lithium therapy was progressively started in a hospital setting (clozapine 300 mg/day; lithium 1350 mg/day). After 15 days a dramatic improvement in mood and psychotic symptoms was evident. After four weeks there was 50% improvement on the BPRS (from 74 to 37). The mean CGAS score changed from 25 to 72. At the CGI-Severity of Illness subscale, a 57% decrease was evident; at the CGI-Global Improvement subscale there was a 75% increase. The only significant side effects were sedation and fatigue, but they were not so severe as to induce a reduction of dosage. The boy was discharged from the hospital after three weeks and successfully returned to school with no modifications in treatment. After a nine-month treatment there was no reoccurrence of psychotic or manic symptoms. The implications of pharmacological therapy in treatment refractory manic episodes with psychotic features are discussed.