This study investigated the forms of inhibin released into the circulation 1) in very early pregnancy, 2) after stimulation of the corpus luteum by exogenous hCG, and 3) in abnormal and failing human pregnancy. Samples were assayed by enzyme-linked immunosorbent assays for inhibin A, inhibin B, and inhibin pro-alphaC-related immunoreactivity (pro-alphaC-RI). The concentration of inhibin A rose steadily during the conception luteal phase to an initial peak 12 days after ovulation (104 +/- 23 pg/mL), then rose rapidly to a further peak 43 days after ovulation 424 +/- 6 pg/mL). The concentration of pro-alphaC-RI exhibited a much larger peak on day 15 after ovulation (1423 +/- 361 pg/mL), but fell thereafter. The concentration of inhibin B was low after ovulation and subsequently barely detectable in pregnancy. hCG treatment resulted in a significant rise in the concentrations of inhibin A and pro-alphaC-RI, but had no effect on the inhibin B concentration. The pro-alphaC-RI concentration was a better indicator of continuing pregnancy viability than either hCG or inhibin A. Early trophoblast secretes proportionately more bioactive inhibin than the corpus luteum. The corpus luteum and trophoblast do not secrete inhibin B into the circulation. These data support the concept of different physiological roles for different inhibin forms.