Primary cultures of visceral yolk-sac (VYS) endodermal cells were used to assess the effects of teratogenic and nonteratogenic antibodies. When assessed by cytotoxicity assay, teratogenic antibodies appeared to be lethal to the cultured cells at high concentrations (1.25-5 mg of antibodies per ml of culture medium). At a nonlethal dosage, the teratogenic antibodies induced morphological changes, including retraction and rounding up of living cells. The cytotoxic effect as well as the effect on cell morphology appeared to be dose-dependent and specific to VYS endodermal cells. The mechanisms of cell killing were not the same as those attributed to complement-mediated cell lysis. The nonteratogenic antibodies did not have any cytotoxic effect nor did they cause any cell morphological alterations. The results of this investigation, when interpreted by correlating the dose-dependent effects of the teratogenic antibodies on cultured endodermal cells with the in vivo teratogenic effect, suggest that teratogenic antibodies when given at a teratogenic dose cause congenital abnormalities without killing the VYS endodermal cells.