In this prospective longitudinal study, plasma androgen levels were determined during 1-7 years in 45 patients aged 5.6-23.8 years with either isolated growth hormone (GH) deficiency or multiple pituitary hormone deficiencies. Dehydroepiandrosterone sulfate, dehydroepiandrosterone, delta 4-androstenedione and testosterone were measured by RIA in 339 blood samples collected during the study period. Mean plasma androgen levels are normal in isolated GH deficiency. Patients with multiple pituitary hormone deficiencies, but normal ACTH reserve, have mean levels lower than normal. Patients with multiple deficiencies including ACTH deficiency have still lower plasma androgen levels. Longitudinal analysis of the data, however, shows that patients with either isolated GH deficiency or multiple pituitary deficiencies without ACTH deficiency constitute a heterogeneous population, with either normal or low to very low plasma androgen levels. Treatment with human GH as such does not have any effect on the adrenal androgen secretion. A dissociation is found in some patients between adrenarche and gonadarche, which indicates that the two events are not controlled by the same mechanisms. Our results support the existence of a specific hypothalamic-pituitary adrenal androgen-stimulating hormone (AASH). ACTH, although not identical to AASH, is essential for normal adrenarche. Induced puberty with estrogens in girls does not influence plasma androgen levels, and pubic and axillary hair growth is not achieved. It is suggested that replacement treatment with dehydroepiandrosterone sulfate should be administered to girls with hypopituitarism and very low plasma androgen levels at the time of the induction of puberty. Finally, it appears from this study that, to interpret the plasma androgens in hypopituitarism, body surface is as good as bone age.