We detected a PstI restriction fragment length polymorphism in the 5'-non-coding region of the dopamine D4 receptor gene (DRD4), making it the seventh known polymorphism for DRD4. DNA polymorphisms in the putative regulatory region of DRD4 are of interest because of the reported six-fold increase in D4 receptors in post-mortem schizophrenic brain tissue [Seeman P, Guan HC, Van Tol HHM (1993) Nature, 365, 441-445]. We found no difference in the PstI allele frequencies between DSM-III-R schizophrenia patients (0.76 and 0.24, n = 41), and matched control Caucasians (0.77 and 0.23, n = 46). The PstI DRD4 polymorphism has potential use in linkage and association studies with neuropsychiatric and cardiovascular disorders.