We determined whether purified immunoglobulin G from patients with antiphospholipid antibodies causes fetal loss in pregnant mice. Sera were obtained from nonpregnant parous women (group 1) and nonpregnant women with antiphospholipid antibodies and a history of fetal loss (group 2). Pregnant BALB/c mice were given an intraperitoneal injection of 15 mg of IgG on day 8 of pregnancy. Typically, mice treated with IgG from anti phospholipid antibodies aborted within 48 hours. When animals were sacrificed on days 9 to 15, the uterus of each animal was inspected for the presence of live, dead, or resorbing fetuses. In contrast to mice injected with control IgG or saline solution, each mouse injected with IgG from anti phospholipid antibodies aborted and no live fetuses were found (p < 0.05). Histologic examination of the uteroplacental interface showed decidual necrosis in the mice treated with IgG containing anti phospholipid antibodies, and immunofluorescent studies also showed prominent intravascular decidual IgG and fibrin deposition. We conclude that IgG from anti phospholipid antibodies of women with fetal loss causes fetal loss in BALB/c mice. It appears that the fetal loss is mediated by IgG binding in the maternal decidual vasculature. © 1990, Mosby. All rights reserved.