The effect of phenylalanine (Phe) on plasma and brain Phe and tyrosine (Tyr) levels and on short-term food intake in male rats was measured after intragastric (i.g.), subcutaneous (s.c.) and intraperitoneal (i.p.) administration. Compared to equimolar alanine (Ala), which served as the control, Phe significantly suppressed feeding at a dose of 90 mg/kg body wt when given i.p., but doses up to 720 mg/kg body wt had no effect when given i.g. or s.c. The high doses of Phe given by the i.g. or s.c. route resulted in higher levels of Phe in both plasma and brain than those following i.p. injection (90 mg/kg body wt). Furthermore, brain Tyr levels after i.g. Phe (720 mg/kg body wt) were equal to or higher than after i.p. Phe (90 mg/kg body wt). We conclude that the route of administration is an important variable influencing the effects of Phe on feeding behavior, and that these effects are not readily explained by plasma or brain Phe and Tyr concentrations.