Male rats (100 g) previously adapted to a 20% casein diet were fed diets containing from 0 to 55% of casein and were killed after 20, 60, 150, 240, or 330 min. Food intake of rats fed a protein-free diet or a diet containing greater than 35% of casein was depressed within 20 min and remained depressed for up to 5.5 h. Depressed food intake of rats fed protein-free diets was accompanied by a rapid reduction in plasma and brain total concentrations of free indispensable amino acids (IAA). Food intake depression among groups fed diets containing in excess of 35% casein was associated with elevated plasma and brain total IAA concentrations, compared with those of animals fed diets containing 15-20% of casein. No consistent relationships were observed between food or protein intakes and whole-brain concentrations of 5-hydroxytryptamine, 5-hydroxyindole-3-acetic acid, or their sum. Our results suggest that in animals fed a single diet, food intake is depressed if the total concentration of free IAA in brain either falls below a certain critical minimum or exceeds some maximum tolerable level.