Restriction fragment length polymorphism (RFLP) patterns were studied in serologically confirmed DR4-DQ3 positive patients with rheumatoid arthritis by Southern blot analysis using full length cDNA probes specific for DRB, DQA and DQB hybridized with genomic DNA digested with informative restriction endonucleases. The RFLP patterns correlated with serology confirming all patients to be DR4+ve. The DQB1*0302 (DQ8) allele identified by 12.0kb BamHI, 3.3kb Hind III and 1.8kb Taql fragments was present in all patients suggesting them to be DR4-DQB1*0302. Hybridization of Taq 1 and PVU II digested genomic DNA with DQA cDNA probe revealed four informative RFLP patterns. While three of them correlated with known DR4 subtypes, one was a new polymorphism observed specifically in Indian patients with rheumatoid arthritis. The study further indicated that two of the several known subtypes of DR4, viz., DRB1*0401-DW4-DQB1*0302 and DRB1*0404-DW14-DQB1*0302 may be implicated in susceptibility to rheumatoid arthritis in the Indian population.