The prevalence of infection with malarial parasites and the incidence of anaemia and delivery of infants with low birthweight (LBW) were investigated in 575 Malawian mothers who received one, two or three doses of sulfadoxine-pyrimethamine (SP) during pregnancy. All the subjects were enrolled at their first antenatal visit and all delivered at hospital. The prevalence of Plasmodium falciparum infection at first antenatal visit was 35.3% in primigravidae and 13.6% in multigravidae (P < 0.001). Mean haemoglobin concentration was significantly lower in primigravidae than in multigravidae (8.8 v. 9.5 g/dl; P < 0.001). Of the 233 women tested for HIV infection, 18.8% of the primigravidae and 23.7% of the multigravidae were seropositive. At delivery, there was no significant difference in parasite prevalence in peripheral or placental blood between women who had received one or two antenatal doses of SP. The multigravidae who had received two doses of SP had higher mean haemoglobin concentrations than those who had received just one (P = 0.009) [this difference was not seen in the primigravidae (P = 0.92)]. However, linear regression analysis indicated that the haematinic supplements given to the subjects contributed more to this increase in haemoglobin concentration than the SP. The mean birthweights were higher, and incidence of LBW lower in babies born to primi-and multi-gravidae who had received two or three doses of SP treatment than those seen in babies born to women who had had just one dose (P < 0.03 for each). The odds ratio for LBW in primigravidae compared with multigravidae decreased from 3.2 to 1.0 as the number of SP doses increased from one to three. The benefit of three doses (compared with none) was equivalent to the population-attributable risk of LBW in primigravidae being reduced from 34.6% to 0%. Subjects who were seropositive for HIV were twice as likely to give birth to LBW babies as the other subjects. The use of SP was not associated with maternal side-effects or perinatal complications. The present results indicate that multiple doses of SP taken during pregnancy will lead to a highly significant reduction in the incidence of LBW in infants born to primigravidae, even if the women have HIV infections. This reduction is observable even when parasite prevalence at delivery is high because of re-infections in late pregnancy; reduction in parasite prevalence earlier in pregnancy, as the result of SP treatment, leads to improved foetal growth.