Our working hypothesis is that antiphospholipid antibodies, especially antiphosphatidlyserine, are responsible for many of the symptoms of early and severe pregnancy-induced hypertension (PIH) and may contribute to milder forms. Very high levels of antiphospholipid antibodies lead to pregnancy loss before the hypertension can develop whereas lower levels result in a live birth complicated by severe and early hypertension, thrombosis, thrombocytopenia (with elevated antiplatelet antibody levels), severe intrauterine growth retardation, and stroke. The mechanism of action for antiphospholipid antibody-induced PIH is through modulation of the relationship between platelets and vascular endothelial cells resulting in maternal and placental thrombosis and many of the symptoms of PIH. We will investigate the incidence of specificity of antiphospholipid antibodies from PIH patients using serologic reactivity in enzyme immunoassays, purify human polyclonal antibodies of known specificity and produce monoclonal human and mouse antiphospholipid antibodies, and study the effects of these antibodies on in vitro prostacyclin and thromboxane generation and on in vitro protein C activation. In addition, we will develop a rabbit model for antiphospholipid antibody-induced PIH.