Prostaglandins and leukotrienes have been implicated in the pathogenesis of various types of headache, mainly because some, but not all, cyclo-oxygenase inhibitors are effective in their treatment. We have therefore investigated whether a pathologically changed turnover of arachidonic acid (AA)-containing phospholipids can be seen in headache patients, using isolated polymorphonuclear cells (PMNs) from healthy controls and patients with chronic paroxysmal hemicrania (CPH) and cluster headache. PMNs from healthy controls incorporated 55% of the added (1-14C)AA into total lipids, and 0.5% +/- 0.14% of this radioactivity was found in the phosphatidylserine (PS) fraction. PMNs from a cluster headache and a CPH patient showed 300% and 900% increase in PS labeling from AA, respectively. No other phospholipids showed any difference between controls and patients. The results are discussed in connection with membrane signal transduction via the PS-dependent protein kinase C.