Six subjects with distal ampullary ectopic pregnancies were treated with four doses of intravenous methotrexate (1.0 mg/kg) followed by four doses of leucovorin (0.1 mg/kg, intramuscularly). The diagnosis was established in all cases by laparoscopy following sonography and radioimmunoassay for serum beta subunit of human chorionic gonadotropin. Subjects were followed with daily quantitative serum beta-human chorionic gonadotropin radioimmunoassay and sonography. Five of the six subjects experienced resolution of their ectopic pregnancy without additional surgical treatment. One subject underwent salpingectomy following treatment. Morbidity also included three patients with mild stomatitis or gastritis, and two patients had transient elevations of serum transaminase levels. Two patients had protracted courses and received blood transfusions. The most abrupt response and most uncomplicated courses were experienced in the three subjects with initial human chorionic gonadotropin levels below 1000 mIU/ml. This preliminary experience suggests that methotrexate may be an effective alternative for the treatment of early ectopic pregnancy.