An open-label, non-randomized, pilot study has been performed in inpatients in need of treatment with an antipsychotic (risperidone) and an antidepressant (mirtazapine) with the objective to preliminarily assess a possible pharmacokinetic interaction and the tolerability of this combination. A 1-4-week single drug treatment phase (risperidone 1-3 mg bid or mirtazapine 30 mg nocte) was followed by a 2-4-week combined drug treatment phase at unchanged doses. Twelve patients were enrolled, nine of whom were treated with risperidone in the single drug phase. Results of plasma level measurements are available for six patients and indicate that adding mirtazapine to risperidone does not alter steady-state plasma concentrations of risperidone and its 9-hydroxy metabolite. Data from one patient suggest that adding risperidone to mirtazapine does not result in clinically relevant changes in plasma concentrations of either compound. The combination was well tolerated and no major or relevant adverse events were observed. Adding risperidone to mirtazapine probably does not necessitate a change of the dosage of either drug, but more extensive investigations are needed.