Children with acute lymphoblastic leukemia (ALL) recive high doses of glucocorticosteroid as part of their treatment. This may lead to suppression of the hypothalamic-pituitary-adrenal axis, acute adrenal insufficiency, and ultimately to life-threatening conditions. This study explores the adrenal function in 96 children with ALL treated according to common protocols. After cessation of induction glucocorticosteroid therapy, they received hydrocortisone substitution therapy (10 mg/m/24 h) until an adrenocorticotropic hormone test (250 µg tetracosatide) showed a sufficient adrenal response [plasma (p)-cortisol =500 nM]. At the first adrenocorticotropic hormone test, 67% of the patients had adrenal insufficiency. When including these patients in a multivariate model, not adjusting for risk factors, the mean elapsed time between end of induction therapy and adrenal sufficiency was 8.5 months (95% confidence interval: 6.3;10.7). Low 0-minute p-cortisol (P=0.02) and low rise in p-cortisol (P