Pituitary-adrenocortical function was studied in patients with chronic renal failure (CRF) and compared with that in normal subjects. All CRF patients were on chronic hemodialysis. The mean morning plasma total and free (nonprotein bound) cortisol levels were higher in patients with CRF. Episodic secretion of cortisol was studied in plasma sampled every 20 min for 24 h. CRF patients demonstrated normal circadian rhythmicity, as evidence by times of peak secretory activity and number of peaks per 24 h. Mean 24-h plasma total cortixol levels were twice the normal levels in CRF patients. Nine of 10 patients with CRF did not suppress plasma total cortisol levels with 1 mg dexamethasone. Four of 10 patients with CRF suppressed with 2 mg dexamethasone orally for 2 days, 5 patients suppressed after 8 mg dexamethasone administration, and 1 patient with CRF resisted suppression. Hemodialysis did not alter mean 24-h cortisol levels or numbers of secretory episodes but produced a shift of secretory activity into the dialysis time period. These studies show alterations in cortisol dynamics in which increased plasma cortisol levels and dexamethasone resistance coexist with normal circadian rhythmicity.