One thousand eight hundred eighty-seven children born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers, including 1045 infants prospectively followed up from birth, were studied. Intravenous drug use was the most frequent maternal risk factor, although the percentage of women infected by sexual contact increased from 5.8% in 1985 to 28.5% in 1990. Of the 551 first children followed up from birth and older than 15 months of age, 101 (18.3%) acquired infection and seroconverted to HIV-1. Another 31 (5.6%) asymptomatic seronegative children showed the presence of viral markers, for an apparent mother-to-offspring transmission rate of 23.9%. Overlapping results were seen in 22 second-born children followed up from birth. Of 59 sibships with definite infection status, when the first child was infected, 14 (40%) of 35 second children were infected, whereas when the first child was not infected, only 2 of 24 (8.3%) second children were infected. Discordance in HIV-1 transmission was found in 1 of 18 pairs of twins. Univariate and multivariate analyses of possible risk factors for HIV-1 transmission performed on the entire population of children and in the cohort of those followed up from birth were basically in agreement in indicating that the development of symptoms in the mother before delivery and breast-feeding (indeed adopted in only 22 infants in whom HIV-1 infection was identified at birth) were significantly and independently associated with a higher transmission rate. In addition, girls were more frequently infected than boys.(ABSTRACT TRUNCATED AT 250 WORDS)