With the use of the Simpson-Evans-Li assay for corticotrophin (adrenal weight-maintaining activity) it was found that human plasma potentiates the biologic activity of ACTH. ACTH added to ACTH-free human plasma showed detectable activity at a concentration of .005 mU/ml; a concentration 3 orders of magnitude greater was required to demonstrate activity when ACTH was added to saline or plasma protein fractions. A repository effect of plasma did not account for the observed effects, and losses during preparation of sample and injection into animals were the same regardless of the vehicle used. Potentiation was found to be present only in plasma obtained from persons with intact pituitaries and could not be demonstrated in plasma of patients with hypopituitarism. Evidence is presented that growth hormone, gonadotrophins and degradation products of ACTH are probably not responsible. Attempts were also made to identify the origin of the activity; the absence of potentiation from plasma of patients with pituitary insufficiency suggests a pituitary or hypothalamic source of the potentiating activity of human plasma.