The pattern of insulin secretion was studied in 107 normal individuals aged 5 to 50 years. Intravenous glucose tolerance tests were performed on 64 islet-cell antibody negative siblings of diabetic children and on 43 normal adults. Puberty was staged using Tanner's criteria and subjects were grouped as follows: I - stage 1 (n = 22), II - stages 2 and 3 (n = 18), III - stages 4 and 5 (n = 20), IV - adults greater than 17 years (n = 47). Basal and stimulated (incremental 0-10 and 10-60 min areas) insulin responses rose throughout puberty (Groups I-III), declined following puberty until the third decade (Groups III and IV) and then appeared constant thereafter. Insulin levels in the 17.6-22.5 year group were lower than in the 12.6-15 year group (p less than 0.01). Fasting insulin to glucose ratios and incremental 0-60 min insulin to glucose area ratios produced a similar age-related pattern indicating that changes in insulin levels were independent of glucose concentrations. Gender did not affect these changes and multiple regression analysis showed that HLA haplotype sharing did not influence insulin responses in siblings of diabetic patients. Age and pubertal status must be carefully considered when interpreting intravenous glucose tolerance tests from patients suspected of having early abnormalities of carbohydrate metabolism.