PIP: The explanation of marked global variation (between 12 and 65%) in the rate of mother-to-child transmission (MCT) of HIV-1 both in developed and developing countries is inadequate. The risk of MCT ranges from one in eight to one in 1.5 pregnancies. There are marked methodological differences in the case definitions, study designs and diagnostic criteria in the various MCT investigations. Although most HIV-1 MCT appears to occur in the peripartum period, it can also occur in the intrauterine phase or immediately postpartum requiring diagnostic techniques that are not often available. Polymerase chain reaction or in situ hybridization tests for early diagnosis of MCT have been found to lack specificity for both HIV-infected and uninfected infants who are born to HIV-infected mothers and who remain HIV-seropositive during their first year of life. A second explanation for the wide variability derives from the varying case mix of any given maternal cohort. HIV infection during pregnancy and pregnant women with advanced HIV-induced immunosuppression are particularly infectious to their children. A third source of MCT variation results from selection bias in many MCT studies. It is not known whether the only mechanism of transmission in the perinatal period is transplacental or transmission occurs during delivery. Data suggest that delivery via Caesarean section halves the risk of MCT. Antiretroviral treatment (zidovudine) for HIV-infected mothers in the immediate prepartum and intrapartum period, followed by postpartum administration to their infants has reduced these infants' chance of MCT by as much as 50%. A recent study from Malawi demonstrated that HIV-1-seropositive women with vitamin A deficiency had a twofold greater risk of transmitting HIV-1 infection to their infants. The many biologic reasons for the wide variation in MCT make it unlikely that prevention will be possible through a single biologic and/or pharmacologic approach.