Studies of ammonia intoxication, orotic acid excretion and L-amino acid feeding regimens have provided new insights into the biological function of arginine. Recent data in near adults of carnivorous species raise doubts about the widely held view that arginine is needed in the diet only for optimum growth and that adults of mammalian species meet their arginine needs from endogenous synthesis. Orotic acid excretion and its suppression by arginine show that liver injury by carbon tetrachloride, ethanol, galactosamine and partial hepatectomy perturbs ammonia detoxication pathways and adds evidence that orotic acid excretion may be useful in detecting liver injury and elevations of tissue ammonia. These forms of liver injury also cause aberrations in metabolism of mitochondria, the site of the first two enzymatic steps in urea synthesis. This review discusses the influence of dietary arginine on insulin secretion, glucose tolerance and repletion of lean body mass in animals. Evidence now available gives reason to question the tenet that arginine is not required by human infants and shows that arginine supplies may be inadequate in a number of disease states. Experimental models now available provide new opportunities for studying arginine needs in Reye's syndrome and other disorders of ammonia intoxication.