Survival in fresh water or mixtures of less than 50% sea water by the euryhaline teleost, F. heteroclitus was reduced by hypophysec-tomy. Average survival time in fresh water was 6-7 days after transfer for sea water adapted fish. Preadaptation in fresh water before operation merely prolonged somewhat the maximal survival time. Death was preceded by symptoms of asthenia, a slight weight increase averaging 4.3%, and a fall in blood serum chloride from 0.850 g% NaCl found in normal fish in fresh or sea water and in hypophysectomized fish in sea water to about 0.383 g%. Replacement therapy with Fundulus pituitary brei enabled the hypophysectomized fish to survive in fresh water. Pituitary extract from Perca flavescens, a strictly fresh water species, was partially effective in promoting survival, whereas extracts from glands of Pollachius virens, a marine species, had no beneficial influence. Injections of ACTH, GH, TSH, thyroxin, DOCA, posterior lobe extract, and an ACTH - TSH -GH combination failed to enable the fish to survive in fresh water. Hypophysectomy was shown to have no effect upon the cytology of the chloride cells of the gills either in the active (sea water) or regressed (fresh water) condition. Mucous cells, normally more abundant in the gills of fresh than of salt water -adapted fish, were found to be severely atrophied in hypophysec-tomized fish of both environments.