Previous work in this laboratory has shown that passive immunization of mice against early pregnancy factor (EPF) leads to failure to maintain pregnancy. The findings presented in this paper demonstrate that this treatment affects the development of the embryos very early in gestation. By Day 3, 54 and 25% of embryos in the 2 groups treated with anti-EPF immunoglobulin (Ig)G and IgM, respectively, had not developed to the 4-cell stage, compared with 12 and 1% in the control groups. None of the embryos in the mice treated with anti-EPF had developed beyond the 8-cell stage. A similar delay in development after treatment was observed on Day 4. The effect apparent during the early stages of cleavage is an indirect rather than a direct one, as 2-cell embryos (32-36 h post coitum), cultured in vitro in the presence of anti-EPF antibodies, developed uninterrupted to the morula and blastocyst stage. The delay in development did not appear to be caused by a disruption of the normal pattern of circulating progesterone, as progesterone concentrations on Day 4 were within the normal range for Quackenbush mice.