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Racial differences in the incidence and natural history of insulin-dependent diabetes mellitus were evaluated in Allegheny County, Pennsylvania. The yearly incidence rate for whites was approximately 1.5 times that for blacks. The cumulative risk of developing insulin-dependent diabetes prior to age 20 was greater for whites (3.1/1,000, males; 2.8/1,000, females) than for blacks (1.7/1,000, males; 2.0/1,000, females). There was a slight excess risk for white males versus white females (relative risk = 1.09, p = 0.04), while no sex differential in risk was noted for blacks. The temporal trends and seasonal patterns were similar. Blacks more frequently possessed human lymphocyte antigen (HLA)-DR3/X and whites DR4/X; however, the risks associated with these antigens were similar by race. At onset, blacks had evidence of greater immunologic disturbance and less frequently reported infection than whites, although blacks more often had evidence of previous coxsackie viral infections. Evaluation of mortality patterns by race revealed that blacks had a higher mortality rate than whites. By 20 years duration of diabetes, blacks had a 2.4-fold increase in the risk of mortality compared with whites.