The distribution of three polymorphisms of the mu opioid receptor gene (OPRM1) was investigated in four different Asian populations, and in heroin-dependent subjects deriving from three of these populations. For the A118G polymorphism, we found significant differences in allele and genotype frequencies between different ethnic groups and highly significant association with heroin dependence in Indians for both genotype distribution (p = 0.024) and allele frequency (p = 0.009). For the C17 T polymorphism, the minor allele was documented in Chinese and Malays for the first time. Molecular haplotyping revealed complete linkage dis-equilibrium between the A118G and C17 T polymorphisms. Linkage disequilibrium between the A118G and C1031G polymorphisms was found to be almost complete in all four ethnic groups.