Single i.v. doses of beta-phenylethylamine (PEA) and its N-methyl homolog (NMPEA) were administered to separate groups of five dogs. The dose- and time-related effects of these compounds were determined on pupil diameter, heart rate and body temperature. Blood samples were obtained concurrently with the physiologic measures and plasma levels of PEA and NMPEA were determined by gas chromatography. Both compounds dilated pupils, tended to produce an initial tachycardia followed by a bradycardia and elevated body temperature. The plasma pharmacokinetics of both PEA and NMPEA could be described by first-order kinetics which estimated half-lives of approximately 5 to 10 min. Plasma levels for both amines correlated significantly only with increases in pupil diameter. The present findings demonstrate that the endogenous trace amine PEA and NMPEA, which may be produced enzymatically by nonspecific N-methyl transferases, produce prominent physiologic effects of short duration when administered i.v. in the dog, suggesting that alterations in the metabolism of these amines which result in elevated plasma levels can produce pronounced effects on mammalian nervous system function.