Alcoholism and substance abuse have been associated with a polymorphism in a noncoding region of the D-2 receptor gene (the Al allele of the Taq1 'A' system) in several,(1-9) but not all(10-13) studies. In addition, the presence of the A1 allele has been associated with lower density of D-2 receptors in the caudate nucleus in one postmortem study.(14) If the Taq1 'A1' allele is in linkage disequilibrium with a mutation that decreases the expression of the D-2 receptor gene, it is conceivable that subjects with the A1 allele might be predisposed to behaviors which stimulate dopamine transmission, such as alcoholism or substance abuse. In this study, we attempted to confirm the association between the A1 allele and lower D-2 receptor density, and explored a possible association between the B1 allele and D-2 receptor expression, Genotypes at the Taq1 'A' and 'B' systems were determined in 70 subjects who underwent in vivo measurement of D-2 receptors-binding potential with single photon emission computerized tomography (SPECT) and the selective dopamine D-2 receptor radiotracer [I-123]IBZM. [I-123]IBZM-binding potential was identical in A1 carriers (ie, subjects heterozygous or homozygous for that allele) (230 +/- 85 ml g(-1), n = 27) and A1 noncarriers (231 +/- 70 ml g(-1), n = 43), Similarly, we found no effect of the B1 allele on [I-123]IBZM-binding potential. In conclusion, the results of this study failed to replicate the previously reported association between A1 allele and lower D-2 receptor expression.