An attempt was made to ripen the uterine cervix in 100 high-risk pregnancy patients (pregnancy between 34 to 41 weeks' gestation), with the use of intracervical instillations of 0.25 mg of prostaglandin E2 mixed with a tylose gel. The maturation process was repeated every 48 hours. Forty-nine patients were delivered of infants after the first maturation and 51 patients required between two and nine instillations. In patients requiring multiple instillations, the mean delay between the first procedure and delivery was 9 +/- 4 days (range, 2.4 to 16 days). Among the 59 nulliparous women, only 23 were delivered of infants after a single maturation and 36 required multiple maturations (p < 0.02). When the group of patients who were delivered of infants after a single maturation process was compared with the group requiring multiple maturations, no difference could be seen with regard to age, term of pregnancy, or Bishop cervical score at the time of inclusion in the study. The myometrial activity and the onset labor induced by prostaglandin E2, were similar in both groups. Fetal heart rate decelerations occurred in 16.3% (8/49) of the patients with single maturations and in 17.6% (9/51) of the patients who required multiple maturations. The outcome of the pregnancy and the rate of cesarean sections (24% and 27%) were similar in both groups. No patients required cesarean sections because of failed induction of labor. Cervical ripening after repeated applications of 0.25 mg of prostaglandin E2 seems to be safe for the fetus, providing that the patient is closely supervised.