The adrenolytic agent, 2,2-bis[2-chlorophenyl-4-chlorophenyl] 1,1 dichloroethane (o,p'-DDD), was used over a 20-month period following surgery in a 2 3/12-year-old girl for treatment of adrenocortical carcinoma. The child remained free of disease and was maintained on glucocorticoid and mineralo-corticoid supplements for 7 years. Hormonal evaluation was undertaken at 9 9/12 years of age to determine remaining adrenal steroidogenic capacity. Following discontinuation of both hydrocortisone and 9 alpha-fludrocortisone, she remained stable and asymptomatic. Immediately after discontinuing 9 alpha-fludrocortisone, the adrenal glomerulosa was able to respond to stimulation by the renin-angiotensin system as shown by the ability to achieve renal sodium conservation on a restricted sodium intake (less than 10 mEq/d for 5 d). The response of the adrenal fasciculata to ACTH stimulation showed a slower recovery. Baseline levels of cortisol were in the low normal range, but there was no increase in plasma cortisol or urinary 17-hydroxysteroids following stimulation with ACTH. The responses of cortisol, deoxycorticosterone, and corticosterone to ACTH stimulation gradually improved to achieve normal stimulated levels 18 months after stopping medications. Serum testosterone and delta 4-androstenedione were initially increased for level of puberty, while levels of dehydroepiandrosterone were prepubertal. Testosterone and delta 4-androstenedione did not suppress with dexamethasone (2 mg/d for 2 d; 4 mg/d for 2 d), and dehydroepiandrosterone decreased only slightly. However, administration of norethindrone (Norlutin) (10 mg orally, three times a day for 3 d) resulted in suppression while human chorionic gonadotrophin (hCG; 5000 U i.m. daily for 3 d) produced stimulation of testosterone, delta 4-androstenedione and dehydroepiandrosterone. Thus the androgens were felt be predominantly of ovarian origin. Dehydroepiandrosterone rose to low normal levels by 18 months after discontinuation of hydrocortisone. We thus demonstrate for the first time that both the adrenal glomerulosa and fasciculata have the capacity to recover normal function following treatment with o,p'-DDD. Further, we suggest that early exposure to excess adrenal androgens may result in mild alteration of gonadal function.