A cohort of 570 untreated pregnant women from Burkina Faso was studied to assess the influence of epidemiologic factors on malaria infection, which was quantified as the mean of serial, season-adjusted parasitemia measurements (mean parasite density [MPD]) carried out during the last five months of gestation. A significant effect of the area of maternal residence on the MPD was found (P < 0.003) and was probably due to geographic differences in mosquito transmission conditions. The strong relationship observed between parity and malaria infection (P < 0.0001), with MPD levels decreasing as the number of gestations increased, confirms that primigravidae are a high-risk group whose protection should be a priority. After adjustment for two relevant epidemiologic factors (i.e., area of residence and parity), the residual MPD values fitted a mixture of two distributions. This result supports the view that a major gene is involved in the determination of malaria infection intensities and is consistent with the results of a recent familial study in Cameroon.