Phenylethylamine can initiate migraine-type headaches in susceptible individuals. Migraine sufferers have a reduced ability to deaminate all monoamines, but particularly phenylethylamine. Phenylethylamine readily crosses the blood-brain barrier and thus could be a mediator of the cerebrovascular disturbances seen in migraine attacks. Cerebral blood flow was measured in 15 anesthetized baboons by the intracarotid 133Xe clearance technique. Phenylethylamine (4 x 10(-7) moles.kg-1min-1) produced significant increases in cerebral blood flow (36 percent) and cerebral oxygen consumption (45 percent) during the first 40 minutes of infusion. In contrast, an increased phenylethylamine concentration (2 X 10(-6) moles.kg-1min-1) constricted the cerebral bed (cerebral blood flow reduced by 28 percent). The response of the cerebral circulation to hypercapnia was preserved during the infusion. Phenylethylamine thus is capable of producing in an experimental animal a pattern of cerebrovascular events similar to those seen in migraine.