We tested the hypothesis that in migraineurs, there is hypofunction of the cerebral vasodilator purinergicsystem, which utilizes ATP and other adenine nucleotides as neurotransmitters. Besides being present inneuronal vesicles, ATP exists in a uniquely sequestered form in the dense bodies of platelets which are amodel for the study of neuronal vesicular function. Platelet ATP-release and aggregation were measured inwhole blood by the newly developed impedance technique using collagen and epinephrine as inducingagents. Consistent with other reports, no responses were seen with epinephrine. With collagen induction,aggregation was nearly equal in controls and migraineurs. However, ATP-release was significantly lowerin migraineurs with the higher collagen concentration. Stepwise logistic regression predicts that for each100 unit decrease in ATP-release, the chances of being a migraineur increases by 1.89. We believe thatdecreased platelet ATP-release is a marker of migraine reflecting hypofunction of the purinergic system,and as a result a relatively greater tendency for vasoconstriction which predisposes to migraine attacks.