Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP) concentration and headache intensity were investigated in 19 female migraineurs during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was administered 120 min after the onset of the attack. Blood samples were obtained immediately before and 60 min after sumatriptan administration. In those subjects whose migraine attack improved considerably 60 min after the treatment the plasma CGRP concentration decreased significantly (P < 0.05). In contrast, plasma CGRP concentration failed to change in patients whose headache did not improve. In addition, plasma CGRP concentrations showed significant positive correlations with the headache scores both 60 and 120 min after sumatriptan administration (P < 0.05). According to our results plasma CGRP concentration decreases parallel to headache intensity during sumatriptan treatment and this decrease in CGRP predicts effectiveness of antimigraine drug therapy. This supports that one of the main effects of triptans is to decrease CGRP release.