A number of interactions of the atypical antipsychotic clozapine with other drugs are well known, some of which can be attributed in part to the pharmacokinetic interactions associated with cytochrome P450 enzymes during drug metabolism. Clozapine is mainly metabolized by the cytochrome P450 isoenzyme 1A2. The proton pump inhibitor omeprazole can induce CYP1A2. We report on two patients with schizoaffective disorder who received omeprazole in addition to clozapine because of gastrointestinal complaints. Before the co-medication with omeprazole was started, the patients had been receiving clozapine for 78 and 41 days and for 40 and 8 days at a stable daily dose of 325 mg (patients 1 and 2, respectively). The co-medication with omeprazole was associated with a reduction in the plasma levels of clozapine of 41.9 % and 44.7 %, respectively, in these patients. The decrease in the plasma concentrations of clozapine in the presence of omeprazole might be due to the induction of the cytochrome P450 isoenzyme CYP1A2. If patients are receiving omeprazole as co-medication, close monitoring of plasma clozapine levels is recommended. If clozapine levels drop, the drug should be adjusted accordingly. If necessary, an alternative to omeprazole should be chosen.