Effect of deficiency in endogenous arginine synthesis was studied in connection with NO synthesis and blood pressure. Rats with massive resection of small intestine were fed an arginine-free diet (AF rats) for 24 days. Control rats were pair-fed an isonitrogenous and isocaloric arginine-replete diet. AF rats lost weight by a mean of 28 g whereas control rats kept original weight. Urinary excretion of nitrate and cGMP was reduced in AF rats by about 40% after the feeding. Blood pressure became elevated by 20-25 mmHg in AF rats after the feeding. The concentrations of arginine in muscle and plasma of AF rats were reduced to 17 and 39%, respectively, of control rats. AF rats may be a novel animal model for the in vivo study of NO.