Objective: Our aim was to assess the efficiency of methotrexate therapy for unruptured ectopic pregnancy. Study design: From November 1990 to December 1996, 60 patients diagnosed with unruptured ectopic pregnancies were treated by the Departamento de Ginecologia y Obstetricia at the Hospital Virgen Macarena of Seville. Of these, 14 patients received an intrasacular injection of 15 mg of methotrexate, 45 were given an intramuscular dose of 50 mg/m(2) and only one received the drug by both routes. Results: Forty-six patients (76.7%) responded successfully to treatment. Of these, 10 had been given the drug intrasacularly (10/15, 66.7%), while 36 had received the drug intramuscularly (36/46, 78.3%). Twenty patients (33.3%) had minor side effects, the most frequent being mild abdominal pain. Falling levels of leukocytes on the third day after initiation of treatment may serve as a fairly accurate criterion to predict the patient's response to the treatment. Conclusion: Our data support the use of methotrexate therapy as a reliable alternative to surgical intervention in the treatment of unruptured ectopic pregnancy. Intramuscular administration, without laparoscopy, appears to be the most convenient route as it is easily implemented and has comparatively few complications. (C) 1998 Elsevier Science Ireland Ltd.