Previous reports suggest that peptides containing an amino acid sequence similar to that of ACTH-(4-10) increased Na excretion in the rat. gamma 2MSH contains such a sequence. An in vivo rat bioassay for natriuretic factors was employed to demonstrate the natriuretic action of gamma 2MSH. A significant natriuretic effect was observed, with a peak response 30-50 min following the bolus injections of 0.64, 6.4 or 64 pmol, but not with smaller or larger amounts of gamma 2MSH. A kaliuretic and diuretic action of gamma 2MSH was not consistently evident. gamma MSH may represent an endogenous compound involved in the physiological regulation of Na excretion.