The dose-response relationship between plasma ACTH and plasma cortisol was examined in normal subjects, patients with Addison's disease and patients with Cushing's disease. Plasma cortisol and ACTH levels were measured every half-hour from 06.00 h to 10.00 h and from 16.00 h to 18.00 h during a control day and during 1 to 3 days of continuous cortisol infusion. A plot of mean morning plasma ACTH versus the log of mean plasma cortisol revealed a similar dose-response relationship in normal and Addisonian subjects. Total plasma cortisol was four times more potent in suppressing mean morning ACTH in normal and Addisonian subjects, than in patients with Cushing's disease. When plasma cortisol was undetectable, there was no significant difference between mean morning ACTH concentrations in Addisonian patients and in adrenalectomized Cushing's patients. The glucocorticoid feedback control of ACTH in Cushing's disease had dose-response characteristics similar to those in Addison's disease and normal subjects, except for decreased sensitivity to cortisol feedback suppression of ACTH.