AIMS:: Clozapine treatment of schizophrenia is effective only in 30–60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia. PATIENTS & METHODS:: In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR. RESULTS:: Homozygosity for the T825 allele was more frequent among nonresponders (χ = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (χ = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression. CONCLUSION:: Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment.