The dopamine D4 receptor (DRD4) is a candidate gene in the search for a genetic etiology of schizophrenia and for pharmacogenetic factors in the response to antipsychotic treatment. Previous work has not found linkage or association of a polymorphism in exon 3 of this gene with diagnosis of schizophrenia or response to clozapine. In this study we examined this association in Israeli schizophrenic subjects treated with clozapine, compared to ethnically matched controls. Another polymorphism of this gene, in exon 1, was also studied. Both polymorphisms showed no association with schizophrenia or treatment response. A significant difference in allelic distribution of DRD/ exon 3 polymorphism was found between Ashkenazi and non-Ashkenazi control subjects.