Studies were conducted to determine whether interactions occur among dietary lysine, arginine and monovalent minerals in rainbow trout. In one experiment, rainbow trout fingerlings were fed diets containing three levels of lysine (2.4, 3.1 and 3.8 g per 100 g diet), two levels of arginine (1.7 and 2.5 g per 100 g diet) and two mixtures of Na⁺ K⁺ and Cl in a 3×2×2 factorial design. The mixtures varied in the proportions of cations to anions such that Cl equalled the sum of Na⁺ and K⁺ (cations − anions = 0 mEq/kg diet) in one mixture and exceeded the sum of Na⁺ and K⁺ (cations − anions = −200 mEq/kg diet) in the second mixture. Growth and efficiency of feed conversion were not affected by dietary lysine and arginine in fish fed diets containing − 200 mEq/kg balance, but when fish were fed diets containing a 0 mEq/kg balance, 3.8% lysine and a combination of 3.1% lysine and 2.5% arginine depressed both measures of response. Trout receiving the 0 mEq/kg cation-anion balance had significantly higher free histidine concentrations and lower free lysine concentrations in muscle and higher hepatic arginase activity (P≤0.01) than those receiving −200 mEq/kg. In another experiment, trout were fed diets containing three levels of K⁺ (21, 191 and 360 mEq/kg), two levels of Na⁺ (21 and 191 mEq/kg) and two levels of Cl⁻ (179 and 347 mEq/kg) in a 3×2×2 factorial design. Growth and efficiency of feed conversion were depressed and hepatosomatic index increased with higher levels of dietary K⁺ (P≤0.01), Na⁺ (P≤0.05) and Cl (P≤0.01), with significant K⁺ x Cl⁺ (P≤0.01) and K⁺ x Na⁺ x Cl (P≤0.05) interactions. Increasing dietary K⁺ resulted in increased levels of muscle free histidine and decreased levels of muscle free lysine and arginine (P≤0.01), while increasing dietary Cl increased muscle free lysine, the effect of which was dependent on dietary potassium (K⁺ x Cl⁻, P≤0.01). It is concluded that dietary levels of K⁺, Na⁺ and Cl⁻, irrespective of overall cation-anion balance of these minerals, affects growth rate, efficiency of feed utilization and the metabolism of basic amino acids in tissues of trout. Excess lysine causes depressed growth and efficiency of feed utilization. These effects were due to a lysine toxicity rather than a lysine-arginine antagonism, as they were not prevented by supplemental dietary arginine.