Possible involvement of receptors in the pathogenesis of schizophrenia has been suggested. In this study we searched systematically for polymorphisms in the 5-franking region of the 1 receptor. Genetic variation in this region could reduce the expression of the gene, and this suggestion is compatible with findings of reduced binding sites in several cortical regions of schizophrenia. We confirmed G-241T and G-240T polymorphisms; these two consecutive polymorphisms were resolved to be in complete linkage disequilibrium with each other by single-strand conformation polymorphism (SSCP) analysis. We also identified the A61C (Gln2Pro) polymorphism, which was in almost complete linkage disequilibrium with G-241T/G-240T. There was no significant difference in the distribution of alleles or overall genotypes of the polymorphisms between schizophrenic patients (n = 129) and controls (n = 140). We found slight increased homozygosity for T-241/T-240 and C61 in patients compared with controls using multiple comparison (p = 0.045). However, the significance did not remain when a Bonferroni correction was made (p = 0.135). These results do not support that the 1 receptor gene plays a major role in the pathogenesis of schizophrenia.