We measured methionine-enkephalin (MET) in platelets and platelet-poor-plasma of drug-free patients with classic migraine, common migraine or tension headache (TH). Migraineurs were studied both between and during attacks. TH patients were characterized by low platelet-MET and high plasma-MET levels, whereas migraine patients showed high platelet-MET and reduced plasma-MET levels. During migraine attacks both platelet and plasma-MET concentrations increased considerably. We suggest that determination of MET levels in platelets and plasma may be a useful marker to discriminate between TH and common migraine. The rise in MET during attacks may be directed against the ictal increase of serotonin.