Hyperandrogenism secondary to hypersecretion of ACTH in patients with congenital adrenal hyperplasia is frequently a problem in therapeutic management. Despite the use of steroids and antiandrogens, virilism often persists. This paper reports the beneficial effects of cyproheptadine in two adult patients with C-21 hydroxylase deficiency who had persistently increased secretion of androgens while on supraphysiologic doses of prednisone. When cyproheptadine was administered in addition to steroids, plasma androgen levels, ACTH, and urinary 17-ketosteroid and pregnanetriol excretion rates returned to normal and clinical improvement was observed. Discontinuation of cyproheptadine therapy in one patient resulted in prompt recurrence of hyperandrogenemia, which was again ameliorated with reinstitution of the drug. From these findings, I conclude that while glucocorticoids are the mainstay of management of virilizing congenital adrenal hyperplasia, cyproheptadine may be an effective adjunct in some patients with this disorder.