beta-Phenylethylamine and phenylethanolamine are biogenic amines structurally related to amphetamine which are known to occur endogenously in trace amounts in mammalian brain. The purpose of the present experiments was to determine whether these endogenous biogenic amines, like amphetamine, have reinforcing properties. Dogs surgically prepared with i.v. catheters were permitted 4-hr daily access to i.v. infusions of beta-phenylethylamine, phenylethanolamine, N-methylphenylethylamine, cocaine or d-amphetamine under a fixed-ratio one-response schedule of reinforcement. In dogs which had not previously self-administered drugs, the number of infusions self-administered per session of beta-phenylethylamine, N-methyl phenylethylamine and cocaine increased above that for saline typically within 5 to 10 sessions. Increases in the number of injections per session were observed in only two of five dogs with phenylethanolamine, and in only three of five dogs with d-amphetamine within as many as 20 to 40 sessions. Does-effect curves were determined in dogs which had been trained previously to self-administer drug and whose daily drug intake was stable. The relative potencies of these compounds in maintaining self-administration behavior during the 4-hr session were d-amphetamine greater than cocaine greater than phenylethanolamine greater than or equal to N-methyl phenylethylamine greater than or equal to beta-phenylethylamine. These data indicate that the endogenous trace amines beta-phenylethylamine, phenylethanolamine and the N-methyl homolog of beta-phenylethylamine can function as reinforcers and are compatible with hypotheses that they may play a physiological role in the reinforcement process or in neuropsychiatric disorders.