Concordance for Type 2 (non-insulin-dependent) diabetes was determined in 250 monozygotic and 264 dizygotic white male twin pairs who participated in the National Heart, Lung, and Blood Institute Twin Study. These twins were born between 1917 and 1927 and were identified from military records without regard to disease status. We examined surviving members of the cohort twice–at mean ages of 47 and 57 years–and obtained 1-h post-load glucose tests and medication histories. Diagnostic criteria for Type 2 diabetes included a glucose value greater than or equal to 13.9 mmol/l or current use of antidiabetic medication; possible Type 1 (insulin-dependent) diabetic twins were excluded. A strong genetic predisposition to Type 2 diabetes was suggested by 3 lines of evidence from the second examination: (1) 58% of monozygotic co-twins of diabetic twins were themselves diabetic compared with an expected prevalence of 10%; (2) only 1 of 15 originally disease-discordant, monozygotic twin pairs remained discordant for diabetes; and (3) 65% of non-diabetic monozygotic co-twins of diabetic twins had elevated glucose values. Because concordance for diabetes was less than 100% for twins aged 52-65 years and because twins varied in age at onset of disease, non-genetic factors may also influence diabetes development. Among the 19 monozygotic twins pairs discordant for diabetes, diabetic twins did not differ from their non-diabetic co-twins in obesity, diet, alcohol consumption, or education. However, compared with unrelated non-diabetic twins of the same ages, non-diabetic co-twins of diabetic twins gained more weight as adults (p less than 0.02) and had higher glucose levels (p less than 0.03).