The pharmacokinetics of an extemporaneous 25-mg suppository formulation of sumatriptan were compared to those of the marketed 25-mg oral tablet. Sixteen healthy volunteers enrolled in this open-label, two-way crossover study. Fifteen subjects completed the study. The pharmacokinetics of the suppository and the oral tablet were significantly different. Tmax was observed at 0.5 hours in 12 of 15 subjects with the extemporaneous suppository, compared with the range of 0.75 hours to 1.5 hours in 13 of 15 subjects with the oral tablet. The mean Cmax and area under the plasma concentration time curve were 5.4-fold and fourfold greater for the suppository than for the oral tablet. Both formulations were well tolerated, with mild headache experienced in only three subjects. Based upon its pharmacokinetic profile, the extemporaneous suppository may represent a useful alternative therapeutic administartion route for some patients.