Background. To compare the efficacy and side effects of extra-amniotic prostaglandin F2 alpha with intracervical misoprostol for midtrimester termination of pregnancy. Methods. Forty women were randomized to receive either intracervical misoprostol or extraamniotic proslaglandin F2 alpha for termination of pregnancy for congenital abnormalities or intrauterine fetal death. Induction-abortion interval and the incidence of side effects were analyzed for both groups. Results. All women in the PGF2 alpha group; aborted within 28 hours, 16 (80%) of which aborted within 20 hours. Medical termination of pregnancy was complete in 13 cases (65%). In the misoprostol group; all women aborted within 20 hours, 18 (90%) of which aborted within 13 hours. Medical termination of pregnancy was complete in 17 cases (85%). The induction to abortion intervals for the extra-amniotic PGF2 alpha and intracervical misoprostol were 16+/-5.9 hours, and 10.3+/-4 hours (mean+/-s.d.) respectively. This was statistically significant (p=0.001). The incidence of prostaglandin-associated pyrexia, vomiting and diarrhea were significantly increased in the PGF2 alpha group (p<0.05). Abdominal pain was similar in both groups. There was no post-abortive hemorrhage or infection. Conclusions. Misoprostol is an effective, easy to use, safe and cheap drug for termination of second trimester pregnancy. Intracervical administration of misoprostol appears to be effective and well-tolerated with less side effects and no complications. Larger, randomized comparative studies should be carried out to assess its potential advantages.