Objective:To determine the prognostic value of a single serum progesterone measurement for resolution of ectopic pregnancy following methotrexate therapy.Methods:All patients attending our infertility clinic had quantitative &bgr;‐hCG and serum progesterone measured prospectively within the first week of missed menses. Ectopic pregnancy was diagnosed nonsurgically by poorly rising &bgr;‐hCG levels and lack of evidence of intrauterine gestation by transvaginal sonography. Once diagnosed, candidates received a single intramuscular injection of methotrexate, 50 mg/m2. Treatment outcome was categorized as either resolved or requiring surgery, and interpreted with respect to serum progesterone measured within 24 hours of methotrexate administration.Results:Twenty‐one patients were treated for ectopic pregnancy. Eleven had serum progesterone levels greater than 10 ng/mL and ten patients had levels of 10 ng/mL or less. The two groups did not differ significantly with respect to age, weight, hCG at the time of methotrexate administration, or amount of methotrexate administered. Of the 11 patients with serum progesterone levels above 10 ng/mL, only five had pregnancies that resolved following methotrexate. All ten patients with levels less than 10 ng/mL had resolution. This difference is significant (P= .009, 95% confidence interval 0.26‐0.84). There was no improvement in the prediction of outcome when either the absolute or daily percentage increase of hCG was determined before methotrexate administration.Conclusion:A single serum progesterone measurement above or below 10 ng/mL is useful for predicting resolution of tubal pregnancy with methotrexate treatment.(Obstet Gynecol 1994;83:1033‐7)