Among the adverse effects arising from chronic high-dose glucocorticoid treatment, adrenal insufficiency secondary to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluate the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given high doses of dexamethasone as part of their induction chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.