The question whether clinically normal adrenal cortical function can be satisfactorily checked by laboratory studies during substitution treatment with adrenocortical hormones was investigated in 39 patients with adrenal insufficiency. The routine measurement of serum cortisol levels (2 to maximally 7 hours after the morning dose of hydrocortisone or cortisone acetate) revealed marked individual variations which were relatively independent of the morning dosage. Similar extreme variations were found for free urinary corticoids in 24-hour urine. Both values could not be correlated with the clinically individualised and satisfactory long-term substitution dosage and cannot be used, therefore, in the customary manner to assess a normal hormonal state. It appears unlikely that such information can altogether be obtained from plasma levels.