To find out whether subclinical autoimmunity precedes onset of nonfamilial insulin-dependent diabetes mellitus (IDDM), 4806 schoolchildren aged 5-19 years from a township in Holland were followed-up for at least ten years after blood was sampled for measurement of islet-cell antibodies (ICA). ICA positivity conferred a relative risk of IDDM of 533 (95% CI 145-1955). In the 10 years of follow-up 4 of the 8 ICA-positive subjects became insulin dependent, whereas the probability of being free of IDDM was 99.9% for those who were ICA-negative at the start of the study. The findings suggest that, although chronic autoimmunity involving the pancreatic beta-cells may precede non-familial IDDM by many years, a positive ICA test on a single occasion predicts the development of IDDM in only 4 out of 8 subjects over a period of 10 years.