DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second andor third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The M s p I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the BaZ I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distributions of the M s p I and BaZ I genotypes were not independent in 297 individuals (x2 = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the BaZ I polymorphism and allele 2 of the M s p I polymorphism (x2 = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the BaZ I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-IIkR chronic schizophrenics and 85 controls (x = 5.3, df = 1, P = 0.02) and found more important in males than in females. The presence of the BaZ I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts,