719 first-degree relatives of diabetic children were followed up to assess the value of HLA haplotype sharing and of islet-cell antibodies (ICA) for prediction of insulin-dependent diabetes (IDDM). Within a maximum of 8 years' follow-up (3384 patient-years of observation) 16 unaffected relatives (5 parents and 11 siblings) became insulin dependent. The cumulative risk of becoming insulin dependent by age 25 was 16% for siblings sharing two HLA haplotypes with the proband, 9% for those sharing one haplotype, and zero for those sharing none. 13 of 24 (54%) subjects positive for complement-fixing ICA on three or more occasions became insulin dependent, as against 1 of 30 (3%) with noncomplement-fixing ICA alone and 2 of 665 (0.3%) ICA-negative subjects; by life-table analysis the risks after 8 years of known ICA status are 76%, 3%, and 0.6%, respectively. In terms of total time at risk ICA-positive family members had a relative risk of 75.2 compared with ICA-negative individuals. With positivity for complement-fixing ICA the relative risk was 188.5.