1. The functional integrity of the hypothalamo-pituitary adrenal (HPA) system was assessed in rats after prolonged treatment with tetracosactrin.2. Adrenal size and sensitivity to corticotrophin were increased.3. Both the circadian rhythm and the stress-induced increase in HPA activity were inhibited. The circadian rhythm recovered before the response to stress.4. Tetracosactrin given after betamethasone treatment delayed the return of a normal HPA response to stress.5. Suppression of HPA activity appeared to be the result of a direct action of tetracosactrin and not entirely due to the elevations in the plasma corticosterone concentration which it caused.