Structural neuroimaging techniques have consistently shown that treatment of schizophrenic patients with conventional antipsychotics causes an increase in basal ganglia volume. However, findings in schizophrenic patients treated with the newer atypical antipsychotic drugs are less consistently reported. To explore this issue, the authors used a whole-brain, unbiased, and automated technique for comparing brain structural features across scans in schizophrenic patients before and after a treatment with the atypical antipsychotic risperidone. T1-weighted images from 11 first-episode neuroleptic-naive schizophrenic patients were processed and analyzed for regions of interest (basal ganglia) by using optimized voxel-based morphometry. Scans were repeated after 3 months of continuous treatment with risperidone. Region of interest-based voxel-based morphometry analyses revealed increases in gray matter volume for the right and left caudate nuclei and for the left accumbens after the treatment with risperidone. Hence, in our sample of schizophrenic patients, treatment with risperidone was associated, in contrast to the findings for other atypical antipsychotics, with an increase in basal ganglia volume. Such discrepancy could be related to the pharmacodynamics of risperidone (the atypical antipsychotic showing the higher affinity for D2 receptors) and the rather high mean doses used in our study (ie, 6.05 mg/d).