The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5 μ M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1'-hydroxybufuralol (IC50 range, 3.5-25.5 μ M). Olanzapine inhibited CYP3A-catalyzed production of 1', and 4'-hydroxymidazolam (IC50 = 14.65 and 42.20 μ M, resp.). In contrast, risperidone (IC50 = 20.7 μ M) and levomepromazine (IC50 = 30 μ M) showed selectivity towards the inhibition of midazolam 1'-hydroxylation reaction, and haloperidol did so towards 4'-hydroxylation (IC50 of 2.76 μ M). Thioridazine displayed a Ki of 1.75 μ M and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce in vivo interactions. However, with this exception, and given the observed Ki values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms in vivo seems limited.