The purpose of this article is to evaluate the effectiveness, side effects, and complications of high dose methotrexate infusion with leucovorin rescue in select patients with ectopic pregnancy. Between January 1991 and November 1994, 28 patients with ectopic pregnancies were prospectively treated with methotrexate (100 mg/m2 intravenous bolus followed by a 200 mg/m2 infusion over six hours) with leucovorin rescue. Twenty-seven of 28 patients (96%) were successfully treated. Only one patient (4%) required a second course of methotrexate to reach a normal hCG titer. One patient failed methotrexate infusion 45 days after treatment at a hCG titer of 12 mIU/mL. No Gynecologic Oncology Group grade 3 or 4 clinical, biochemical or hematologic toxicities occurred. Uterine bleeding and abdominal pain, not requiring transfusion or hospitalization, occurred in 71% and 56% of patients. The authors conclude that high dose methotrexate infusion with leucovorin rescue is a highly effective, well tolerated, nonsurgical treatment for select patients with ectopic pregnancy.