In this investigation the effect of a low potassium environment on the free amino acid pattern of the skeletal muscle tissue of the killifish, Fundulus heteroclitus, has been studied in an attempt to determine if the changes observed in the potassium-deficient rat (Eckel, Pope and Norris, 1954;Iacobellis, Muntwyler and Dodgen, 1956) could also be found in other members of the vertebrate subphylum. Apparently the rat, but not the dog (Iacobellis, Griffen and Muntwyler, 1957), is capable of replacing part of an intracellular loss of potassium ions with organic cations in the form of basic amino acids, provided a sufficient amount of protein is included in the diet. Amino acids which could serve to restore an intracellular cation-anion balance include lysine, arginine, and histidine. All three carry a net positive charge at body pH. This study, therefore, was made to determine if an intracellular organic cation replacement occurs in potassium-deficient Fundulus and, if so, which basic amino acids are responsible for the replacement of the lost potassium. Methods Killifish {Fundulus heteroclitus) were trapped in the brackish water of the Oyster River near Durham early in August of 1958 and transported to the laboratory where they were placed in a large aquarium containing artificially prepared 50% sea water (salinity = 18 parts per thousand). The formula followed was taken from the Marine Biological Laboratory at Woods Hole manual, "Formulae and Methods, IV," 1954. After a three-day period of adjustment, one-half of the animals was left in 50% sea water to serve as controls, whereas the other half was placed in an adjacent aquarium also containing 50% artificial sea water but lacking potassium ions. Control and potassium-deficient animals were maintained on a diet of powdered, crude casein.At the end of a two-week period animals were removed from each aquarium and their tissues prepared for paper chromatography. In order to obtain 10 grams of skeletal muscle tissue in each case it was necessary to sacrifice 7 control Fundulus and 8 potassium-deficient Fundulus. The fish were skinned and filleted. Ten grams of muscle were macerated in a Waring Blendor, using about 100 ml. of 959S ethanol. After 5 minutes of blending at a moderate speed the liquid was heteroclitus." The Biological bulletin 118, 79-83.