Experiments were carried out in order to further delineate the pathophysiology of the fall of plasma 5-hydroxytryptamine (5-HT) during a migraine attack. Platelets from normal subjects were incubated with 14 C-labelled 5-HT, and the release of 5-HT was measured following exposure of these platelets to plasma taken from migraine patients during an attack or at headache-free intervals. Plasma taken during attacks released significantly more 5-HT. It is concluded that factor (s) exist in the serum during migraine attacks, which can cause 5-HT release from normal platelets. The identification of this factor may be important.