The influence of age and sex on the peripheral metabolism of testosterone was studied by giving intravenous tracers of 14C-testosterone to 21 prepubertal children (13 boys and 8 girls), 39 young adults 18-43 years old (23 men and 16 women), and 10 elderly adults 68-86 years old (6 men and 4 women). Studies were also carried out in 2 sexually immature young adults, one 18-year-old 45 XO phenotypic female with gonadal agenesis and one 18-year-old 45 XO, 46 XX mosaic female with gonadal dysgenesis; the latter was restudied after prolonged estrogen-progestagen therapy. Age and sex influences were observed only with respect to the androsterone/etiocholanolone (A/E) ratio; a sex difference in diol metabolite formation was not observed. Prepubertal children showed no sex difference in A/E ratio, which averaged 1.7 +/- 0.28 in boys and 1.9 +/- 0.42 in girls. Young adult men showed a slightly lower A/E ratio, averaging 1.5 +/- 0.10, while females showed a much greater decrease in A/E ratio, to 0.9 +/- 0.09, so that there was a highly significant (P less than .001) sex difference in this age group. The decreased averages were due to disappearance of the higher end of the ranges seen in prepubertal children; the lower limit of the ranges remained the same. Elderly adult men showed a further fall in the A/E ratio, to 1.0 +/- 0.11, and elderly women also showed a further fall, to 0.4 +/- 0.04; a highly significant (P less than .005) sex difference remained. Once again, the fall in average A/E ratio from young adults to elderly adults was due to disappearance of the higher end of the ranges in the former, the lower limits of the ranges were the same in both groups. Of the 2 sexually immature young women, one showed an A/E ratio of 1.3, just below the upper limit for young adult women, and the other showed a ratio of 1.8, well above that limit and thus typical of prepubertal girls. Estrogen-progestagen therapy of the second girl decreased the A/E ratio to 1.4, the upper limit for young adult women. It was concluded that there is a fundamental aging effect in both sexes which causes a gradual progressive decrease of the mean A/E ratio as a result of progressive disappearance of the higher individual A/E values while the lower end of the range of values remains constant; superimposed on this gradual decrease is an acute pubertal decrease in females, probably mediated by the development of the estrogen-progestagen milieu characteristic of sexually mature women.