Recent studies show that obsessive-compulsive symptoms may occur in many patients with schizophrenia and may predict a poor prognosis. Pilot studies have shown that some schizophrenic patients may improve if a serotonin reuptake blocker is added to their neuroleptic. We have performed a pilot, double-blind, crossover study of clomipramine (CMI) or placebo, added to maintenance psychotropic medication. Six schizophrenic patients with obsessive-compulsive symptoms were studied in a double-blind CMI versus placebo crossover protocol. The patients met DSM-III-R criteria for chronic schizophrenia, experienced obsessive-compulsive symptoms, and had been previously stabilized on their psychiatric medication. The patients were rated at baseline and longitudinally through the study with the Positive and Negative Symptom Scale for Schizophrenia (PANSS) and the Yale Brown Obsessive-Compulsive Scale (YBOCS). An analysis of covariance was used to compare the drug versus placebo effect at the final visit with the baseline rating as a covariate. Ratings on both the YBOCS and the PANSS showed that patients improved significantly more on CMI than on placebo. No patients experienced an exacerbation of psychotic symptoms. Preliminary findings from this double-blind, crossover, pilot study of CMI and placebo, designed to assess the effect of CMI in the treatment of schizophrenic patients with obsessive symptoms, suggest that CMI is superior to placebo in the treatment of obsessions and compulsions and improves overall schizophrenic symptoms. Further studies with larger samples and longer follow-up period are necessary to confirm these preliminary findings.