INVOLVEMENT of the cerebral serotoninergic system has been invoked to explain the origin of the pain and the vascular phenomena in migraine. To further investigate the type of cerebral serotonin receptors that may be altered in migraine, the prolactin (PRL) and cortisol responses to m-chlorophenylpiperazine (mCPP), a selective 5-HT1A,-5-HT2A/Creceptor agonist, were monitored in 12 patients suffering from migraine without aura and in 14 matched healthy controls. Each subject underwent two challenges, one with mCPP (0.5 mg/kg) and the other with placebo (orally) using a double-blind crossover design. Anxiety level was measured by the State Trait Anxiety Inventory. Migraine patients had a greater PRL response to mCPP (p= 0.05) and greater anxiety (p< 0.01) than controls; cortisol response to mCPP did not differ suggesting that 5-HT2Creceptors are normal in migraine. Augmented PRL response to mCPP could derive from 5-HT1Areceptor hypersensitivity, perhaps as as a consequence of anxiety due to pain expectation. Cerebral 5-HT1Ahypersensitivity could also explain the increased occurrence of migraine attacks during anxiety.