Among major histocompatibility complex class II antigens, HLA-DR2 appears to have a much larger degree of polymorphism than usually recognized by routine serology or restriction fragment length polymorphisms. We have utilized oligonucleotide probes to further identify the DR2 specificity and its molecular subtypes on the basis of specific DNA sequences as they occur in a select sample from the Asian Indian population. In addition, oligonucleotide typing of HLA-DQA1 and -DQB1 genes allowed us to determine specific associations of DRB1, DRB5, DQA1, and DQB1 alleles in DR2 individuals. A set of 60 oligonucleotide probes were hybridized to polymerase chain reaction (PCR)-amplified DNA from DR2 homozygous or heterozygous individuals. The most common DR2 subtypes that occurred in this selected population are: DRB1*1501 (60%), DRB1*1502 (33.8%), and DRB1*1602 (6.2%). No example of DRB1*1601 was detected. By combining these results with the allelic variations at DQA1 and DQB1, we were able to detect at least seven different haplotypes, the most common being DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 and DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0502. At least five unexpected combinations, not reported among Western Caucasians, were noticed in this sample. Thus oligonucleotide typing is a valuable tool for defining further polymorphisms in the HLA-D region as exemplified by its applications to typing DR2-positive patients with tuberculoid leprosy and pulmonary tuberculosis.