TWO allelic variants of the delta opioid receptor gene, distinguished by a single base exchange T to C in codon 307 of the translated region, were detected in humans. The amino acid sequence was thereby not changed. The resulting C and T alleles combined to give the three genotypes CC, CT and TT. Allele C was more frequent in a sample of 103 German Caucasian heroin addicts (53.4%) than in a control group (39.1%, n = 115). The proportion of CC homozygotes was much greater among the drug-dependent subjects (26.2%) than in controls (9.6%). Although the reasons for this association remain to be explained, our results argue for a participation of the delta type of opioid receptors in the pathophysiology of heroin dependence.