Substance use disorders, particularly those involving alcohol, marijuana, and cocaine, are highly prevalent among patients with schizophrenia and contribute markedly to its overall morbidity. Unfortunately, standard (typical) antipsychotic medications do not seem to reduce substance use in patients with schizophrenia and may even increase it. Recently, however, a few anecdotal case reports and two previous small 'N' surveys have found that clozapine, an atypical antipsychotic medication, seems to decrease substance use in patients treated with this drug for their psychoses. The authors report data from a retrospective survey of substance use in 58 patients treated with clozapine who had a history of comorbid schizophrenia (or schizoaffective disorder) and substance use disorder. Of these 58 patients, 43 were being treated with clozapine at the time of the survey; the remaining 15 patients had discontinued clozapine before the survey. The survey involved chart review and clinician interview to assess change in substance use and global clinical symptoms while receiving treatment with clozapine. More than 85% of the patients who were active substance users at the time of initiation of treatment with clozapine decreased their substance use over the course of clozapine administration. For patients who continued treatment with clozapine up to the present, the decrease in substance use was strongly correlated with a decrease in global clinical symptoms. Data from this retrospective survey further support the previous observations that clozapine reduces substance use among patients with schizophrenic disorders. Moreover, the data suggest the need for prospective controlled studies of the effects of clozapine on substance use in this population.