Several aspects of nitrogen metabolism have been studied in adult nonhyperphagic, hyperinsulinemic, ventromedial hypothalamus (VMH)-lesioned rats. Ten days postoperatively, VMH-lesioned rats had high plasma levels of urea and low plasma tyrosine, while plasma alanine, glutamine, total amino acid, and protein levels were unaltered. Urea production and excretion were increased in VMH-lesioned rats. Increased urea synthesis could not be attributed to enhanced peripheral release of amino acids. In vitro, measurements of hepatic amino acid uptake and liver protein synthesis did not reveal any disturbances of these processes in VMH-lesioned rats. However, hepatic transamination and lipogenesis from amino acids were increased following VMH-lesions. In addition to the hyperinsulinemia previously reported to occur in nonhyperphagic VMH-lesioned rats, this study showed an increased glucagon secretion from perfused pancreases of these animals. These data together suggest that the excess of the two hormones at the portal vein of VMH-lesioned rats would favor uptake and deamination of amino acids, their diversion to lipid synthesis and possibly other pathways, with consequent increase in urea production and reduced supply of amino acids to peripheral tissues available for nitrogen retention.