The physiology of aging in very old people is still poorly understood. A wide variety of age-related factors confuse the interpretation of existing data, especially as regards the modifications of the endocrine system. The effect of age on the gonad-hypophyseal function was studied in 26 over ninety-year-old males and compared with a control aged between 27 and 88, subdivided into age groups. The serum levels of total testosterone were stable up to the ninth decade while they were lower in the over ninety-year-olds; free testosterone and its peripheral metabolites (estrogens and dehydrotestosterone) were also lower in the over ninety-year-olds with respect to the others, although the decrease had started more gradually at about the fourth decade. Sex-hormone-binding-globulin, the main serum carrier of testosterone, increased gradually with age. The levels of hypophyseal gonadotropins were constant up to the ninth decade where a significant and abrupt increase was observed. The data suggest the presence of marked alterations of the testicular-hypophyseal axis in the later decades of life, with important repercussions on the pattern of circulating sex steroids.