To examine the role of heritable factors in insulin-dependent diabetes mellitus (IDDM), we studied the incidence of IDDM in the offspring of patients with the disease who were identified by the medical records of the Joslin Diabetes Center from 1928 to 1939. We found 187 survivors who, after the diagnosis of IDDM, had produced 419 offspring for whom information about diabetes status was available. By the age of 20, 6.1 per cent of the offspring of the 88 men had diabetes; in contrast, only 1.3 per cent of the offspring of the 99 women had the disease by the age of 20 (P less than 0.05). Daughters and sons of the men with IDDM were affected equally (there were insufficient numbers of affected offspring of diabetic women to permit determination of whether the sexes were equally affected). We conclude that IDDM is transmitted less frequently to the offspring of diabetic women than to those of diabetic men. More study is required to determine whether this difference reflects a genetic mechanism or, instead, selective perinatal loss of the affected offspring of diabetic mothers.