1. The rate and quality of improvement obtainable by ACTH therapy in patients suffering from multiple sclerosis is positively related to the quality of concordance between the excretion rates of the 17-hydroxycorticoids and the 17-ketosteroids during the high-dosage phase of ACTH therapy. 2. The quality of concordance between the excretion rates of the 17-hydroxycorticoids and the 17-ketosteroids is a variable independent of other variables known to affect the outcome of ACTH therapy in patients suffering from multiple sclerosis, such as age, sex, and duration and severity of the illness. 3. In a small number of patients studied at necropsy, the zona fasciculata appears to be the major element involved in the ACTH-induced hyperplasia and hypertrophy of the adrenal cortex in patients with type 1 and type 2 steroid concordance. The difference in quality of the adrenocortical steroid responsiveness revealed by study of only 2 steroid excretion rates, namely, those of the 17-hydroxycorticoids and of the 17-ketosteroids, suggests the desirability of systematic studies of other adrenocortical hormones in patients suffering from multiple sclerosis, before and during ACTH therapy and in comparison with normal controls.