With this severely ill patient with treatment-refractory schizophrenia and obsessive-compulsive symptoms, a combination of clozapine and the selective serotonin reuptake inhibitor paroxetine resulted in significant clinical improvement in both psychotic and obsessive-compulsive symptoms. While paroxetine has been reported by some to increase clozapine levels (3), in Mr. A, this did not happen. However, because paroxetine is largely metabolized by the cytochrome P450 IID6 (CYPIID6) enzyme (4) and clozapine is predominantly metabolized by the CYPIA2 and partly by the CYPIIIA enzymes (5), perhaps the lack of increase in his clozapine blood level should not be that surprising. Moreover, we have reported previously on another case (6) in which paroxetine was added to clozapine without affecting blood levels of clozapine. Nonetheless, given the potential interaction, until more data are collected, clozapine levels should be monitored closely during initial phases of paroxetine therapy. In addition, prospective studies are required to fully assess the optimal pharmacological management of patients who have treatment-refractory psychosis with obsessive-compulsive features.