To investigate whether rectally administered misoprostol is an effective treatment for postpartum hemorrhage unresponsive to conventional first-line management. We studied 14 women with postpartum hemorrhage unresponsive to oxytocin and ergometrine (n = 10) or, when ergometrine was contraindicated, oxytocin alone (n = 4). While awaiting carboprost, misoprostol 1000 microg (five tablets) was administered rectally. In all 14 women, the hemorrhage was controlled, and sustained uterine contraction produced within three minutes of administration of misoprostol. Misoprostol appears to be absorbed effectively from rectal as well as oral and vaginal mucosa. Rectally administered misoprostol appears to be an effective treatment for postpartum hemorrhage unresponsive to oxytocin and ergometrine; therefore, it might be an alternative to parenteral prostaglandins or at least minimize the number of women requiring this invasive treatment. Given that it is an inexpensive and stable drug, misoprostol has considerable potential to reduce maternal mortality from postpartum hemorrhage in developing countries.