Antibodies directed against a beta-cell specific antigen with a molecular weight of 37 kDa have recently been described. These anti-37kDa antibodies were measured by the immunoprecipitation technique in individuals at risk for insulin-dependent diabetes mellitus (IDDM), with islet cell antibodies (ICA) greater than 20 Juvenile Diabetes Foundation units (JDFU). These subjects were recruited from large population-based cohorts at various degrees of risk for developing the disease before adulthood. Anti-37kDa antibodies were measured in 25 ICA-positive first degree relatives with ICA greater than 20 JDFU, identified from a baseline cohort of 1,185 relatives (age: 0-75 years). Four relatives were positive for anti-37kDa antibodies since the first determination onwards. These relatives developed IDDM in a 2-year follow-up period. We included 300 children with an IDDM parent, and aged less than 7 years, in a prospective survey for the prediction of IDDM. Five (1.6%) showed ICA greater than 20 JDFU. None of them were found to be positive for anti-37kDa antibodies, and none have progressed to diabetes during a 2-year follow-up. Among a baseline cohort of 13,380 schoolchildren (age: 6-17 years), 28 (0.2%) were found to have ICA greater than 20 JDFU. One boy was positive for anti-37kDa antibodies on two consecutive occasions and developed IDDM after a 10-month follow-up. No other schoolchildren with ICA greater than 20 JDFU were found to be positive for anti-37kDa antibodies. Altogether 40 other ICA-positive sera (with titres < 20 JDFU) were found to be negative for anti-37kDa antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)