The aim of the present study was to analyze retrospectively the safety and success rates of single- and two-dose methotrexate (MTX) protocols for the treatment of hemodynamically stable cases of ectopic pregnancy at University Department of Gynecology and Obstetrics, Zagreb University Hospital Center, during a five-year period. The study evaluated MTX treatment efficacy in 35 women with ectopic pregnancies in relation to the initial levels of human chorionic gonadotropin (hCG) and progesterone. Successful treatment was recorded in 32/35 women, 24/25 on single dose MTX and 8/10 on double dose MTX, whereas 3/35 patients underwent laparoscopy. The mean initial hCG level in all 35 patients on day 0 was 657.54 +/- 592.4 IU/L; 572.99 +/- 488.10 IU/L in those successfully treated with MTX and 1560.30 +/- 890.70 IU/L in those requiring additional laparoscopy (p < 0.005). The mean initial hCG level was 393.10 +/- 305.9 IU/L in patients successfully treated with a single dose of MTX and 973.5 +/- 722.40 IU/L in those with an additional dose of MTX (p < 0.002). The mean initial progesterone level was 16.36 +/-10.70 nmol/L in 35 MTX-treated ectopic pregnancy patients, 13.64 +/- 8.89 nmol/L in those with treatment success and 28.45 +/- 11.32 nmol/L in cases of treatment failure (p < 0.05). The mean level of progesterone on day 0 was 12.74 +/- 830 nmol/L in patients successfully treated with a single dose of MTX and 26.10 +/- 18.80 nmol/L in patients treated with double-dose MTX (p < 0.006). It is concluded that pretreatment values of hCG and progesterone are inversely related to medicamentous treatment success in selected cases ofhemodynamically stable patients, thus they may be used as an important predictor in the management of ectopic pregnancy treated with MTX.