An adrenal cortex adenoma, surgically removed from a female patient with primary aldosteronism, was used to examine the effect of ACTH, angiotensin II, gamma 3-MSH, and the N-terminal fragment of pro-opiomelanocortin purified from porcine anterior pituitaries on aldosterone release in vitro. Primary cultures of tumor cells were incubated as a monolayer in a 96-well microtitration plate and the aldosterone release was measured in the incubation medium after 2 h of incubation in the presence of absence of different concentrations of the peptides. On a molar basis, the N-terminal portion of pro-opiomelanocortin seems to have the highest activity of all of the peptides assayed.