Plasma free alpha hCG, estradiol (E2), and progesterone (P4) concentrations were measured in 38 patients with histologically confirmed ectopic pregnancy (EP). The menstrual gestational ages ranged from 6-10 weeks. Free alpha hCG levels, although significantly lower than those in women with a normal intrauterine pregnancy, increased markedly during this time period, from 1.5 to 11 ng/ml, a 7-fold increase. In women with an intrauterine pregnancy, only 0.6-fold increase occurred during the same time period. Plasma P4 and E2 concentrations in patients with EP were significantly lower, except at 6 weeks for E2 and in the sixth and seventh weeks for P4. The ectopically implanted trophoblast undergoes impairment of its ability to synthesize beta hCG, but not alpha hCG. The lack of utilization of alpha hCG in EP causes it to increase, while the level of intact hCG is low. These observations suggest that the levels of alpha hCG are a sensitive marker for placental well-being, and that it could serve as an additional diagnostic tool for the early diagnosis of EP. The placenta is only partially able to compensate for the reduced ovarian production of E2 and P4.