In malaria-endemic regions, the impact of malaria upon pregnancy and the value of chemoprophylaxis for malaria for pregnant women remain controversial. We prospectively studied 302 pregnant women who presented in labor to Centre Médical Evangélique, Nyankunde, Zaire. We evaluated the incidence of malarial infection in mothers, placentas, and neonates and examined the effect of infection on birth weight and perinatal mortality. We analyzed the outcome of pregnancy in relation to prophylaxis with chloroquine, controlling for parity and prenatal clinic attendance. Peripartum smears of maternal blood (21%), placentas (33%), cord blood (9%), and neonatal blood (7%) were positive for Plasmodium falciparum. Maternal malaria increased the risk of perinatal death (relative risk [RR] = 12.4) and low birth weight (RR = 3.7). Neonatal malaria increased the risk of perinatal death (RR = 7.2). Chloroquine prophylaxis protected against maternal (RR = 0.4) and fetal malaria (RR = 0.2), low birth weight (RR = 0.39), and perinatal death (RR = 0.38). Peripartum malaria increases the risk of perinatal death and low birth weight. Chemoprophylaxis with chloroquine during pregnancy may have a protective effect, even in certain areas where chloroquine-resistant P. falciparum is endemic.