A 46-yr-old phenotypic female with XY genotype presented an unusual form of nonfamilial male pseudohermaphroditism with gynecomastia. Seemingly a normal girl until puberty, the patient developed breasts but became virilized as well at age 13 and failed to menstruate. No uterus was found above the short and blindending vagina. Serum testosterone (T) was subnormal for a male while urinary 17-ketosteroids (17KS) were elevated. The disorder was clarified when increased serum LH concentrations and a 10-fold elevation in serum androstenedione (A) were found. Serum A and estrone (E1) concentrations doubled following HCG stimulation while little change in serum T was observed. Exogenous T suppressed scrum LH by 50% and lowered serum A, E1 and estradiol (E2) to normal or subnormal levels. Dexamethasone suppression and ACTH stimulation studies revealed normal adrenal function. Blood production, metabolic clearance, and A to T conversion rates indicated that 91% of circulating T was derived from A which was produced at a rate of 24.8 mg/24 hr. Testicular arteriovenous differences in A, T, El and E2 concentrations revealed testicular secretion of both A and Et but minimal secretion of T and E2. Following gonadectomy, serum LH and FSH concentrations rose well above their initial levels while A, T, E1 and E2 as well as urinary estrogens fell to subnormal levels and 17KS excretion decreased to normal. Testicular biopsy showed prominent Leydig cells, marked peritubular sclerosis, as well as absence of spermatids and spermatozoa. These results are most compatible with 17β-hydroxysteroid dehydrogenase deficiency.