In the French prospective cohort study we compared the mother-infant transmission rates of human immunodeficiency virus type 1 (HIV-1) and human immunodeficiency virus type 2 (HIV-2). As of January 1, 1994, 86 infants born to 68 HIV-2-seropositive mothers have been included in the cohort. Forty-one children had been followed up for more than 18 months at the time of analysis. During the same period 1758 infants born to 1589 HIV-1-infected mothers were included; 419 mothers were of African origin. One thousand one hundred fifteen children had a follow-up of 18 months or more; 260 of these were of African origin. The HIV-2 transmission rate, based on serologic status at 18 months, was 0% (95% confidence interval, 0 to 11%). This was significantly lower than the HIV-1 transmission rate of 21% (confidence interval, 16 to 26%) in infants born to African mothers. The difference remained significant when the comparison was extended to HIV-1-positive women of French origin infected by the sexual route or by iv drug abuse. Most of the HIV-2-infected women were from West Africa; they were older and had more children than the HIV-1-infected women. The circulating CD4+ lymphocyte count was significantly higher in these women than in the HIV-1-infected mothers. Reported differences in the replication of the two viruses probably account for the lower mother-infant transmission rate of HIV-2.