Objective To investigate the effect of risperidone on regional cerebral blood flow (rCBF) and the relationship between efficacy and rCBF ratio. Methods Twenty four naive schizophrenic patients (diagnosed according to the ICD 10) completed 8 weeks treatment with risperidone. Ten patients were male and 14 were female. Twenty six healthy controls were enrolled as control group. The treatment dose of risperidone was 3~6 mg/d. After 8 weeks treatment, brain imaging was conducted again. Results Before treatment with risperidone, compared to the control group, the baseline rCBF ratios of left and right inferior posterior temporal of patients were higher and the cognitive activated rCBF ratios of left mid-lateral frontal was lower. After treatment, the baseline state rCBF ratios of right lateral temporal, left and right superior posterior temporal were significantly decreased. The cognitive activated rCBF ratios of left and right inferior medial frontal, left inferior lateral frontal, left superior fronto temporal and left superior lateral fronal significantly increased. The efficacy was correlated with changes of the baseline rCBF ratio in some RIOs. Conclusions Risperidone could change the blood perfusion in some ROIs. It suggested that the perfusion in these ROIs could be useful for predicting treatment efficacy.