Placental histopathology was studied in a cohort of 204 women living in an area of low Plasmodium falciparum and P. vivax malaria transmission. Detection of malaria antenatally was active, by weekly peripheral blood smears, and all infections were treated. Significant histopathologic placental malaria changes (increased malaria pigment, cytotrophoblastic prominence, and presence of parasites) were found only in a minority of women who had P. falciparum infections in pregnancy. These changes were significantly more frequent in women with evidence of peripheral blood infection close to delivery and only in these cases were placental inflammatory cells increased. Antenatal P. vivax infection was associated only with the presence of malaria pigment in the placenta. All placental infections diagnosed by blood smear and 32.4% (12 of 37) diagnosed by histopathology were associated with patent peripheral parasitemia. This study indicates that prompt treatment of peripheral parasitemias during pregnancy limits placental pathology. The effect on birth weight reduction may not result from irreversible placental changes but from the acute insult of infection. These findings emphasize the importance of treating malaria in pregnancy promptly with effective antimalarial drugs.