Fifty juvenile insulin dependent diabetes mellitus (JIDDM) patients of Tamil Nadu (South India) were typed for HLA-A, -B, -C, -DR, and -DQ, ESD, GLOI, C3 and HP polymorphisms. The frequencies of B8, DR3, DR4, DR53 and DQ2 antigens of the HLA system were significantly higher in the patients than in controls (relative risk, RR = 4.81; 5.14; 3.98; 3.36 and 2.53, respectively). However HLA-DR2, -DR5 and -DQ1, observed less frequently in the patient group, appear to play a role of protection against the disease (RR = 0.32; 0.30 and 0.20 respectively). HLA haplotype analysis demonstrated very high relative risk associated with two hitherto unreported haplotypes namely A3,DR1 and Cw3,DR4 (RR = 27.30 and 20.00, respectively) and also scanty distribution of the haplotypes A1,B17 and DR2,DQ1 (RR = 0.39 and 0.36, respectively) in the patient group. Among other genetic markers tested, GLOI is informative with its phenotype GLOI 2-1 showing positive association with JIDDM (RR = 4.06).