New indications for misoprostol include medical abortion, cervical softening, induction of labor and treatment of postpartum hemorrhage. Various routes of misoprostol administration under study include oral, vaginal, buccal, sublingual and rectal.This was an open-label, randomized, cross-over study of the pharmacokinetic differences of buccal vs. sublingual misoprostol 800 mug in 10 healthy women.Of the 10 women enrolled, 2 withdrew after experiencing excessive cramping from the sublingual route of misoprostol. The mean misoprostol plasma concentration-time curves at 4 h [area under the curve (AUC)0-4)] and the maximum concentration (C(max)) showed that levels were significantly higher for sublingual administration than the buccal route. Buccal misoprostol administration resulted in fewer symptoms and was found to be more acceptable.Sublingual administration of misoprostol had a higher AUC and C(max) compared with buccal administration. The pharmacokinetics may help to determine the best application of misoprostol depending on the indication.