The D2 dopamine receptor gene (DRD2) displays Taq I restriction fragment length polymorphisms (RFLPs) at two different loci, termed A and B. One of the three different Taq I A 'alleles' described at this site, the A1 allele (size = 6.6 kb), has been found to be associated with alcoholism and with drug abuse in the majority of studies reported to date. A complete map of the Taq I A RFLP site has been constructed, through hybridization with different fragments of the 3' flanking region and polymerase chain reaction (PCR). When screening 432 unrelated individuals to establish possible A1 allelic association with drug abuse or dependence, we have encountered a novel Taq I A RFLP, which we have named 'A4' (size = 8.6 kb). This sequence variant displays a frequency of approximately 1% in our sample and shows a Mendelizing genetic pattern in an Italian nuclear family. Primers suitable for detecting A4 using PCR have been designed. The A4, but not the A3 'allele', displays substantial overlap with the A1. In particular, A2 and A3 share the presence of a Taq I restriction site, whose absence in A1 and A4 is apparently associated with substance abuse vulnerability. Therefore, in association studies it is proper to contrast individuals displaying A1 and A4 RFLP patterns, with individuals displaying A2 and A3 RFLPs.