Phenylephrine HCl was incorporated into feed given to male and female F344/N rats and B6C3F1 mice in studies of 14 days, 12 weeks, and 2 years duration. In 12-week studies, body weight gains decreased with dose, and deaths of male rats and mice occurred at concentrations of 5,000 ppm and above; however, no organ-specific toxicity was evident. During 2-year studies, body weights of rats receiving diets at 620 and 1,250 ppm and mice at 1,250 and 2,500 ppm ranged up to 16% less than control. Survival of high dose male rats was substantially greater than controls. Survivals of other dose groups of rats and mice were similar to controls. Chronic focal inflammation of the liver, and inflammation of the prostate were increased in dosed rats. No increases in neoplasms were observed in rats or mice consuming diets containing phenylephrine HCl for 2 years. The incidences of mononuclear cell leukemia and pheochromocytomas of the adrenal gland were decreased in dosed male rats. Approximate time weighted average doses ranged up to 54 mg/kg/day for rats and 280 mg/kg/day for mice during the 2-year studies.