Leukotriene B4 (LTB4) levels in plasma and its generation in vitro from isolated polymorphonuclearleukocytes (PMN) were measured in migraine and cluster headache patients during and between painattacks. The LTB4plasma levels in cluster headache patients during an attack were significantly higherthan in patients between attacks. There was a positive correlation between the time of sampling from thebeginning of attack and the LTB4level. The LTB4 plasma levels in migraine patients during and betweenattacks did not differ significantly from control levels. The results suggest that LTB4appears rapidly in thecirculation at the beginning of a cluster attack and thereafter declines in amount. LTB4release from PMNwas induced by stimulation with the calcium ionophore A23187. The release of LTB4was significantlyhigher in migraine patients during attacks on stimulation with a submaximal dose of A23187 0.5 μM. LTB4 release induced by A23187 in migraine patients during symptom-free intervals and cluster headachepatients did not differ from healthy controls. LTB4 release was not affected by 5HT and NA inconcentrations up to 10-4M. The results suggest that LTB4is more easily generated in migraine patientsduring attacks. These studies on isolated cells provide a suitable model for the investigation of themetabolism of lipoxygenase derivates in headache patients.