Prostaglandins have been recognized as effective abortifacients for several decades. Misoprostol, a synthetic analogue of prostaglandin E1, has several advantages over other prostaglandins that include low cost, easy storage at room temperature, and favorable side effect profile. In recent years, misoprostol has attracted attention as an effective and cost-efficient agent for the medical interruption of the second-trimester pregnancy. Nowadays, misoprostol has been accepted widely as a safe and effective agent for labor induction during the second trimester. Various doses, routes, and protocols for medical termination of pregnancy during the second trimester have been investigated. The optimal dosage and route of administration, however, have yet to be defined. Previous studies have demonstrated greater efficacy with vaginal misoprostol versus oral administration in effecting mid-trimester termination. However, oral administration of any medication is preferred by patients and health care providers alike. The higher efficacy after vaginal administration may be explained by the pharmacokinetics of the drug. Zeiman et al showed that the systemic bioavailability of vaginally administered misoprostol is 3 times higher than that after oral administration. Plasma concentrations of its metabolite, misoprostol acid, peak one to two hours after vaginal application as compared with the peak seen 30 minutes following oral administration, and although peak levels are lower with the vaginal route, they are sustained longer and overall exposure to the drug is increased, perhaps because of the presystemic gastrointestinal or hepatic metabolism that occurs with the oral route. An additional explanation for the higher efficacy could be that there is a direct effect on the cervix that initiates the physiologic events that lead to increased uterine contractility. The sublingual route of administration has not been reported in the literature prior to 2001. Since then and partly because of issues relating to patient preference, investigators started studying the sublingual route of administration of misoprostol. In theory, the sublingual route could mimic vaginal administration pharmacokinetically, although there have been no such reported studies on this route of administration.