Methotrexate treatment of unruptured ectopic pregnancy is safe and effective and preserves reproductive potential. Previous protocols have required multiple methotrexate doses with or without citrovorum rescue. The purpose of this study was to determine whether patients with an unruptured ectopic pregnancy 3.5 cm or less in greatest dimension could be treated with single-dose intramuscular methotrexate (50 mg/m2) without citrovorum rescue. Thirty-one patients were eligible for this outpatient treatment protocol. One patient withdrew from follow-up, leaving 30 patients (96.8%) in the study group. Patients had a mean age of 28.5 years (range 18-37) and a mean gravidity of 3.0 (range 1-8); nine of 30 (30%) had previously undergone a salpingectomy for ectopic pregnancy. Pre-treatment hCG titers ranged from 130-16,700 mIU/mL (mean 4558). Pre-treatment transvaginal sonography visualized the ectopic in 28 of 30 patients (93.3%) and revealed cardiac activity in six patients. Patients were monitored with hCG titers three times per week for the first week, and then weekly until the hCG was less than 15 mIU/mL. A complete blood count and liver enzymes were obtained before treatment and on day 7. All patients had a continued rise in hCG titer for at least 3 days after methotrexate injection, although all levels began to decline by day 7. No patient required a second dose of methotrexate and no patient experienced any side effects. Twenty-nine of 30 patients (96.7%) were successfully treated. Six of 30 (20%) experienced an increase in lower abdominal pain between days 5-10, and two were hospitalized overnight for observation.(ABSTRACT TRUNCATED AT 250 WORDS)