The aim of this study was to investigate central anti-nociceptive mechanisms of i.v. acetylsalicylic acid (ASA) and oral zolmitriptan (ZOL) in migraine patients and healthy subjects using the 'nociceptive' blink reflex (nBR). Twenty-eight migraine patients received ASA (n = 14, 1000 mg i.v) or ZOL (n = 14, 5 mg p.o) during the acute migraine attack and interictally. Thirty healthy subjects received either ASA or ZOL vs. placebo using a double blind cross over design. nBR was recorded in all patients and subjects before, 60 and 90 min after treatment. ASA and ZOL did not inhibit nBR responses in healthy subjects. Both ASA and ZOL suppressed nBR responses (ASA by 68%, ZOL by 78%) only during the acute attack but not interictally. The data suggest, that the anti-nociceptive effects of migraine drugs on the trigeminal nociceptive processing are different during and outside an acute migraine attack.