Objective: To evaluate medical treatment of interstitial pregnancy. Methods: This series was a retrospective study of medical treatment of interstitial pregnancies which was managed in two French Departments of Obstetrics and Gynecology (Bichat public Hospital, Paris and A. Béclère public Hospital, Clamart, France). Fifteen patients with clear evidence of an unruptured interstitial pregnancy were treated by injection of methotrexate (MTX) or potassium chloride (KCL) without surgery since January 1988. The diagnosis was established either by sonography and laparoscopic confirmation in eight cases or by only transvaginal ultrasound in seven cases. Three out of 15 cases in this series, had a heterotopic pregnancy who were treated by transvaginal ultrasound-guided injection of KCL. Others received systemic MTX injection in four cases, and local MTX injection in eight cases under either laparoscopy or transvaginal ultrasound guidance. Four different protocols of MTX (Ledertrexate R) administration was performed in this series with time: at the beginning of our experience, MTX1 protocol, 15 mg i.m. daily for 5 days was used; and after MTX2 protocol, 1 mg/kg body weight i.m. daily for 4 days; MTX3 protocol, 1 mg/kg body weight intratubal associated with 1 mg/kg body weight i.m. daily for 3 days; and now MTX4 protocol, only intratubal 1 mg/kg body weight is especially used. The success was defined as declining serum human chorionic gonadotropin (hCG) to undetectable levels, and no further surgical management was required. Outcome of subsequent fertility was also evaluated. Results: Complete resolution was obtained in 13 (86.6%) out of 15 interstitial pregnancies. Two out of 15 patients, with medical treatment's failure required secondary surgery. No severe side effects of medical treatment were observed. Follow-up hysterosalpingography was performed in 12 patients showing 91.7% tubal patency on the side of interstitial pregnancy. Outcome of intra-uterine pregnancy of the three patients who had heterotopic gestation, was two miscarriages and one delivery at term. Out of the other 12 patients in this series, nine became pregnant within 1 year: eight pregnancies at term, and one induced abortion. At present, among the last three patients, two have no desire to conceive. Conclusion: Our results suggest that unruptured interstitial pregnancies now can be managed with local MTX administration of 1 mg/kg body weight under transvaginal ultrasound or under laparoscopy procedure. This approach is particularly attractive in these patients, where the only alternative to therapy is laparotomy with cornual resection.