Oral prostaglandin E2 (PGE2) was used alone or synergistically with intravenous oxytocin to induce labor in 84 women whose pregnancies were at high risk. A control group of 84 similar high-risk pregnancies where labor was induced with intravenous oxytocin alone was studied to compare the safety and efficacy of the two regimens. Oral PGE2 administration, combined with the synergistic effect of intravenous oxytocin, is safe for induction of labor in gravid women whose fetuses are at risk. Uterine polysystole, which is potentially dangerous, especially to the high-risk fetus, was not commonly encountered and only once was associated with transient fetal bradycardia. Uterine hypertonus was not encountered with PGE2; however, it did occur with oxytocin stimulation. Nausea and vomiting occurred in one third of the women treated with PGE2 but were well tolerated and required discontinuation of the drug in only one instance. There was no apparent advantage of using the combination PGE2 regimen in patients whose cervices were more favorable for induction of labor (Bishop score, 5 to 9). However, oral PGE2, used either alone or synergistically with oxytocin, appears twice as effective in inducing labor than was oxytocin alone in women in whom labor was considered to be "difficult to induce" (Bishop score, 0 to 4). © 1976.