Acute medical illness may produce dramatic changes in endocrine function Although cortisol levels rise in acute medical illness, changes in adrenocortical function and reserve have not been well documented in medical ICU patients. We evaluated plasma ACTH and cortisol levels, and cortisol response to intravenous ACTH in 40 acutely ill patients and 20 anxious but nonacutely ill controls. A wide range of plasma cortisol values (212 to 8430 nmol/L) was observed. More severely ill patients did not necessarily have higher plasma cortisol values. Patients who survived hospitalization had lower mean initial and post-ACTH cortisol levels than patients who succumbed. ACTH levels varied widely and correlated poorly with levels of plasma cortisol. There was no evidence of occult adrenocortical insufficiency. We conclude that plasma cortisol elevations are common in acute medical illness.