To examine the epidemiology and natural history of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), especially genetic and intrapartum exposure factors, we obtained data on twins and triplets born to women infected with the virus. 40 investigators in nine countries contributed demographic, clinical, and epidemiological data on 100 sets of twins and 1 set of triplets. Among the 66 evaluable sets, HIV-1 infection was more common in first-born than in second-born twins (p = 0.004). In 22 sets, only one twin was infected (18 first-born, 4 second-born). 50% of first-born twins delivered vaginally and 38% of first-born twins delivered by caesarean were infected, compared with 19% of second-born twins delivered by either route. HIV-1 infection status tended to be concordant in more monozygotic (14 of 17 sets) than dizygotic (26 of 43) sets, but the frequency and clinical signs of HIV-1-related disease were similar in only 3 of the 10 sets with both children infected. These findings suggest that some infants may be infected in utero before labour but that a substantial proportion of HIV-1 transmission occurs as the first twin encounters the cervix and birth canal. Such measures as cleansing of the birth canal and caesarean delivery before membrane rupture might reduce the risk of transmission for infants born to HIV-1-infected women and should be the subjects of controlled clinical trials. Caesarean section should not be regarded as a wholly preventive measure, however, since substantial proportions of both first-born and second-born twins delivered in this way were infected.