OBJECTIVE: This study investigated the effect of the 102-T/C polymorphism in the 5-HT2A receptor gene on risperidone efficacy. METHOD: One hundred Han Chinese patients with acutely exacerbated schizophrenia were given risperidone for up to 42 days. The patients were genotyped for 5-HT2A polymorphisms. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale while the patients were taking risperidone. Generalized estimating equation methods were used to analyze the effects of treatment duration, T/C genotypes, and other prognostic factors on Positive and Negative Syndrome Scale performance. RESULTS: Patients with the C/C genotype had lower total scores, negative subscale scores, and general psychopathology scores but not positive subscale scores on the Positive and Negative Syndrome Scale than patients with the 102-T/C genotype. Patients with the T/C and T/T genotypes had comparable total and subscale scores. The number of previous hospitalizations and the dose of risperidone also affected Positive and Negative Syndrome Scale total scores. CONCLUSIONS: These results suggest that variations in the 5-HT2A receptor gene may influence individual responses to risperidone.