Consumption of high protein or artificially imbalanced diets induces the expression of the amino acid degrading enzyme histidase (Hal). Glucagon has been postulated as an important physiological regulator of Hal gene expression, however, it has not been demonstrated if serum glucagon concentration is associated with the type and amount of protein ingested. The purpose of the present work was to study histidase activity and mRNA concentration in rats fed diets containing adequate (18%) or high (50%) concentrations of casein, isolated soy protein, or zein as a source of protein, and whether these changes are associated with the plasma concentration of glucagon and insulin generated by the ingestion of these diets. With this aim, 6 groups of rats (n=10 each) were fed in a restricted schedule of 6 h (900 to 1500 h) for 10 d one of the experimental diets: 1) 18% casein, 2) 50% casein, 3) 18% soy, 4) 50% soy, 5) 18% zein, and 6) 50% zein. On d 10, five rats of each group were anesthetized with carbon dioxide and killed by decapitation at 0900 h (fasting), and then five rats were killed after giving the experimental diet for one hour (1000 h). At the end of the experimental period, hepatic histidase activity and mRNA concentration, and serum glucagon and insulin were measured. Rats fed 50% casein or soy diets showed higher histidase activity than the rest of the groups studied. Rats fed 50% zein diets had higher Hal activity than rats fed 18% casein, soy or zein diets, but lower than rats fed 50% casein or soy diets. Hal mRNA concentration followed a similar pattern to that of Hal activity. Hal activity showed a significant association with serum concentrations of glucagon. Serum glucagon concentration was significantly correlated with protein intake. Thus, the type and amount of protein consumed affects Hal activity and expression through changes in serum glucagon concentrations. The results of this study show the physiological role of glucagon in the catabolism of amino acids.