The need for a functional classification of Leydig cell tumors in men with congenital adrenal hyperplasia (CAH) is exemplified by the present case of a 19 yr old boy with this disorder, who developed bilateral testicular masses despite replacement with hydrocortisone. During basal conditions, in which he received hydrocortisone, 25 mg/day, urinary 17-ketosteroids and pregnanetriol were 33 and 18.5 mg/24 h, respectively. Mean plasma 17-hydroxyprogesterone (17OHP) concentrations, 32.2 (a.m.), 58.8 (p.m.) ng/ml, were increased 30- to 50-fold, while mean plasma cortisol (F), 7.7 (a.m.), 12.3 (p.m.) .mu.g/dl, testosterone (T), 485 (a.m.), 493 (p.m.) ng/dl and estradiol (E2), 12.4 (a.m.), 16.3 (p.m.) pg/ml, concentrations were within normal limits. Episodic fluctuations of plasma T, E2 and 17OHP were demonstrated in morning and afternoon samples, with pulses occurring at approximately 90 min intervals. Plasma LH [luteinizing hormone] levels, pulsatile in the morning, fell in the afternoon with no evident episodic release. Mean morning plasma LH was significantly higher than that of afternoon. Following 48 h of ACTH suppression with dexamethasone mean plasma 17OHP and F concentrations fell to 1-2 ng/ml and 2-3 .mu.g/dl, respectively. Mean afternoon plasma T and E2 concentrations decreased (29%) with pusatile fluctuations preserved, and mean afternoon plasma LH concentration increased 4-fold and episodic release was reestablished. Peaks of plasma LH preceded those of T, E2 and 17OHP by 30 min. Six days of ACTH suppression with dexamethasone resulted in a fall of urinary 17KS and pregnanetriol to 12.3 and 4.3 mg/24 h, respectively. The enlarged testes decreased to normal size after ACTH suppression with dexamethasone. During adrenal stimulation with ACTH the testes reenlarged and spermatic venous F (14.3 .mu.g/dl) and 17OHP (557 ng/ml) were 3-fold higher than simultaneous peripheral levels of F (5.2 .mu.g/dl) and 17OHP (196 ng/ml). Light microscopic and EM findings of the tumor were consistent with Leyding cells although no Reinke''s crystals were observed. In the normal testicular tissue, seminiferous tubules revealed maturation arrest of germ cells at spermatocyte level. These data suggest that the functional capacity of Leydig cell tumors in CAH may not correlate with morphological appearance, that such tumors may secrete F and demonstrate ACTH dependence, and that endogenous suppression of LH secretion may occur during periods of inadequate ACTH suppression.