Zolmitriptan is a potent selective 5HT1B/1D receptor agonist for acute migraine therapy. Zolmitriptan has vasoconstrictor activity in cerebral vessels and may cause slight elevations of blood pressure in subjects without hypertension. Therefore, the pharmacokinetics and pharmacodynamics of zolmitriptan (5, 10, and 20 mg) were evaluated in 16 patients with mild to moderate hypertension (controlled by hydrochlorothiazide 50 mg once daily) and 17 healthy age- and sex-matched control subjects in a randomized, placebo-controlled, double-blind, four-period crossover study. The pharmacokinetics of zolmitriptan and its metabolites were dose proportional. Although area under the concentration-time curve (AUC0-infinity) and maximum concentration (Cmax) were slightly higher in patients with hypertension at all doses, this was only statistically significant for AUC at the 20-mg dose. Differences between subjects with and without hypertension were not clinically significant. Zolmitriptan produced a small increase in blood pressure, but this was similar in subjects with and without hypertension and was of no clinical significance. Zolmitriptan was well tolerated in both groups. Zolmitriptan plasma concentrations were higher in women than in men, with higher values of AUC and Cmax and lower total clearance in women. These results indicate that zolmitriptan can be administered for treatment of migraine in patients with controlled hypertension without dose adjustment.