This open-label, parallel-group study assessed pharmacokinetics and tolerability of zolmitriptan, a 5-HT1B/1D agonist for the acute treatment of migraine, and its active metabolite, 183C91, in adolescents compared with adults. Twenty-one healthy adolescent and 18 healthy adult volunteers (with and without history of migraine) received a single 5-mg dose of zolmitriptan. Mean ages were 14.5 years (range 12-17) for adolescents (13 girls, 8 boys) and 39.1 years (range 18-65) for adults (12 women, 6 men). The area under the curve (AUC) and highest observed plasma concentration (Cmax) of zolmitriptan were similar in both age groups; the half-life was 3.01 hours in adolescents versus 3.75 hours in adults. The AUC and Cmax of 183C91, however, were 36% and 39% higher in adolescents, respectively; the half-life was similar in both age groups. Adverse events were similar in both groups in terms of nature, intensity, and frequency. Exposure to zolmitriptan was not significantly different in adolescents compared with adults, but a shorter half-life in adolescents suggests faster elimination in this age group. Exposure to 183C91 was higher in adolescents, suggesting that formation of the metabolite is at least one of the elimination routes of zolmitriptan that occurs at a faster rate in adolescents.