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The present studies demonstrate that the administration of pharmacologic amounts of ACTH is associated with small but significant increases in urinary cyclic AMP excretion and in urinary cyclic AMP/creatinine ratios which are most likely related to a release of cyclic AMP from adrenocortical tissue. Acute suppression of the pituitary-adrenal axis with dexamethasone and stimulation with metyrapone, however, is not associated with changes in urinary cyclic AMP excretion. These results suggest that physiological levels of ACTH and cortisol contribute little, if any, to the urinary excretion of cyclic AMP in man.