In this prospective study of infants born to human immunodeficiency virus (HIV) seropositive mothers, neonatal and maternal characteristics of infected and noninfected infants were compared to determine the factors that may be associated with or contribute to vertical transmission of HIV. Of 134 infants entered as newborns in the study, 31 have definite serological and/or clinical evidence of infection and 103 are considered noninfected (transmission rate, 23.1%). Significantly more of the infected infants had birth weights below 2,500 g (48.4% versus 22.3%), and more infected infants were found to be small for gestational age (16.2% versus 5.8%). A greater number of infected infants experienced two or more problems in the neonatal period than noninfected infants (51.6% versus 24.2%). The incidence of confirmed and suspected bacterial infections was also significantly increased in the infected group. Multiple logistic regression analysis indicated low birth weight had the strongest association with vertical transmission of HIV. There was no significant difference between the two groups in mean maternal age at first pregnancy, mother's marital status, education, type of family, or past history of type of substances abused. Mothers who transmitted HIV to their infants had a trend towards a higher frequency of clinical chorioamnionitis (16.1% versus 5.8%), reported sexually transmitted diseases during pregnancy (45.2% versus 22.3%), and continued illicit drug use (67.7% versus 49.0%). In this group of infants, low birth weight, poor intrauterine growth, neonatal infections and possibly maternal chorioamnionitis, STDs during pregnancy, and continued drug use are associated with vertical transmission of HIV.