If a woman becomes infected with Plasmodium falciparum during pregnancy, her health and that of the fetus and newborn infant are at risk. In 1986, the WHO recommended that pregnant women use chloroquine chemoprophylaxis as a means of preventing the adverse effects of malaria. Today chloroquine resistance is widespread, and malariologists are attempting to produce a vaccine that will protect pregnant women. Unfortunately, little is known about why some women experience severe malaria during pregnancy and others do not, or why the incidence of spontaneous abortions, stillbirths, premature deliveries and low birthweight babies are increased by malaria infection. It is likely that changes within the placenta occur that contribute to retarded fetal development. In the studies described herein, we propose to test the hypotheses 1) that there is a relationship between high parasitemias in the placenta and increased risk of altered fetal development; 2) that high parasitemias occur in the placenta because it is a specialized immunologic environment where parasite-specific immune responses are suppressed; 3) alternatively, that women with unsuccessful pregnancies are infected with a more virulent strain of malaria than those with successful pregnancies; 4) that within the placenta parasites induce the synthesis of tumor necrosis factor (TNF) which alters antigenic expression of syncytiotrophoblasts resulting in reduced fetal retention; and 5) that the presence of parasites sequestered in the placenta can be detected in women who are blood-smear negative by detecting soluble malarial antigens in their serum or urine. Basic information from the proposed studies should help in the development of a vaccine that reduces fetal and infant mortality, as well as identify a method for accurately diagnosing malaria in pregnant women.