The effects of various CYP2D6 genotypes on the steady-state plasma concentrations (Css) of risperidone and its active metabolite, 9-hydroxyrisperidone, were studied in 85 Japanese schizophrenic patients (27 men and 58 women) treated with 6 mg/d risperidone for at least 2 weeks. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using liquid chromatography–tandem mass spectrometry. The patients had the following CYP2D6 genotypes: wild-type (wt) /wt (40 patients), CYP2D6 * 10 (* 10)/ wt (28), CYP2D6 * 5 (* 5)/ wt (8), * 10/ * 10 (5), * 5/ * 10 (3), and CYP2D6 * 4/CYP2D6 * 14 (1), respectively. The Css values of risperidone and 9-hydroxyrisperidone were corrected to the median body weight of 58 kg. The medians (ranges) of the Css of risperidone in the aforementioned genotype groups were 2.2 (0.37–35.7), 6.4 (2.1–26.5), 12.3 (4.7–39.5), 19.4 (13.4–26.4), 64.0 (41.6–68.8), and 91.8 nmol/L. Those values for risperidone-to-9-hydroxyrisperidone ratio were 0.03 (0.01–0.33), 0.06 (0.03–0.19), 0.14 (0.07–0.29), 0.28 (0.25–0.38), 0.48 (0.38–0.58), and 2.35, respectively. The Css of risperidone was significantly (P < 0.05 or P < 0.001) different among the four genotype groups (wt/wt, * 10/wt, * 5/wt, and * 10/ * 10), except between the * 5/wt and * 10/ * 10 groups. Also, the risperidone-to-9-hydroxyrisperidone ratio significantly (P < 0.005 or P < 0.001) differed among these genotype groups. No significant differences were found in the Css of 9-hydroxyrisperidone and the active moiety (the Css of risperidone plus 9-hydroxyrisperidone) among these genotype groups. This study confirms previous findings that the CYP2D6 status affects the Css of risperidone via its strong regulation of 9-hydroxylation of risperidone. However, similar active moiety of risperidone among different genotype groups suggests that the determination of the CYP2D6 genotype has little importance for clinical situations.