The D4 dopamine receptor is of great interest for research into neuropsychiatric disorders and psychopharmacology in light of the fact that it binds the antipsychotic medication clozapine with higher affinity than does any other dopamine receptor [Van Tol, et al., Nature 1991; 350:610-614]. Furthermore, in the third exon of this gene, there is an unusual 48-bp repeat sequence polymorphism that produces variable receptor protein sequences that have different affinities for the drug clozapine [Van Tol, et al., Nature 1992; 358:149-152]. A new two-allele PCR-based SmaI restriction fragment length polymorphism (RFLP) was revealed at the human DRD4 locus employing a new method for the detection of PCR-able RFLPs. The polymorphic SmaI restriction site is located in the 5' noncoding region of the human DRD4 gene. This SmaI PCR-RFLP serves as an additional marker for genetic linkage and association studies between DRD4 and neuropsychiatric disorders.