The frequency of HLA A, B, and DR antigens as well as the Bf and C4 allotypes have been investigated in insulin-dependent diabetes mellitus (IDDM) and compared to that of healthy controls in the Tunisian population. An increase of A30, DR3, DR4, BfF1, C4Ao, and C4Bo and decrease of B40, DR2, DR5, and DR6 were found in diabetics when compared to the value observed in controls. The strongest association was noticed with HLA DR3 and DR4. Heterozygotes DR3 DR4 were very frequent in diabetics: 24.2 per cent versus 3.6 per cent in controls (relative risk 7.72). The protective role of DR2 and DR5 antigens were also confirmed. No supratypes of HLA, Bf, and C4 alleles associated with IDDM have been observed among these Tunisian patients.