Regulation of the expression of the DRD3 gene in the mesolimbic reward system of the brain by cocaine implicates that DRD3 polymorphisms may be associated with the risk for dependence on other highly rewarding drugs of abuse. Homozygosity at a single nucleotide polymorphism leading to the presence of either serine or cysteine in the ninth amino terminal position has been found associated with opiate addiction in a case-control study with moderate sample size from France (Duaux et al., 1998). Subsequently, this finding has not been confirmed in larger samples from Israel (Kotler et al., 1999) and China (Li et al., 2000) that also included unrelated comparison subjects. Results of a replication study in a sample of over 200 heroin-addicted patients and their parents from Germany will be reported. This family-based design safeguards against the effects of population structure that may have been present in prior studies.