HLA-DR and HLA-DQ allele frequencies in four populations (Brahmin, Maratha, Gujarati Hindu Patel, and Parsi) of Bombay, western India, were analyzed using TaqI RFLPs detected by the cDNA probes DRB, DQB, and DQA. Although the overall differences in the HLA-DR and HLA-DQ genotype frequencies among the populations were not statistically significant, several population-specific haplotypes were significant. Multivariate analyses using data on 2 loci (HLA-DR and HLA-DQ) produced a meaningful pattern of genetic affinity and differentiation that parallels the analysis made when frequency data on 23 loci (21 blood group and protein loci and 2 class II antigen loci) are used. The RST for class II loci was 0.006; the genetic differentiation increased to 0.01 when data on 23 polymorphic loci were analyzed. The genetic affinity analysis shows the isolated nature of the Parsi and close genetic affinity between the two local populations of Bombay. Although the RFLP technique has several limitations compared with newly defined PCR-based methods, our analysis shows that the RFLP technique is still a useful adjunct method for studying HLA polymorphisms for which only limited data from the populations of the Indian subcontinent are available.