Latvian insulin-dependent diabetes mellitus (IDDM) patients (n=101) and healthy controls (n=111) were analyzed for HLA-DR and DQ polymorphism. DR3-DQ2 and DR4-DQ8 were positively associated and DR15-DQ6, DR13-DQ6, DR1-DQ5 and DQ7 negatively associated with the disease. The incidence of IDDM in Latvia is very low (6.5 per 100,000) compared to Sweden (24.4 per 100,000), even though Latvia is close to Sweden. The reasons for the decreased incidence are not clear. When the negatively associated DQ were taken together in the healthy controls, more than 75% of the healthy controls were positive for one of the four negatively associated DQ molecules. The excess frequency of the negatively associated DQ molecules in the general population could explain the lower incidence of IDDM in Latvia. Association of HLA-DR and DQ genes with autoantibody markers shows DR3, but not DQ2, to be increased in GAD65 antibody-positive compared to antibody-negative patients. This association was not observed with ICA512 antibodies.