Multiple factors influence the rate of HIV-1 maternal transmission. We examined the possibility that the level of HIV-1 provirus within blood CD4+ T cells may be a critical factor involved in maternal transmission. We developed a quantitative PCR based method to examine proviral load within blood mononuclear cell of HIV-infected pregnant women. HIV-1 proviral load, determined at the time of delivery, was compared in three groups: mothers who transmitted virus to their infants (n=14), mothers who did not transmit virus (n=14), and mothers who received zidovudine according to the ACTG 076 protocol and did not transmit (n=12). The three groups did not differ significantly with respect to maternal age, disease stage, or CD4+ T cell counts. There was no evidence of HIV-1 provirus within blood monocytes in any of the mothers. Mothers who transmitted HIV had significantly higher (p=0.008) provirus levels within their blood CD4+ T cells as compared to non-transmitting mothers (2207 +/- 1626 infected CD4+ T cells/106 cells versus 69 +/- 30 infected CD4+ cells/106, respectively). Mothers receiving zidovudine had a high viral load (2486 +/- 2194 infected cells/106 cells) that did not differ significantly from the untreated groups. Our results indicate that HIV-1 proviral load can be used to predict whether or not mothers are likely to transmit HIV-1 to their offspring. Furthermore, zidovudine does not appear to reduce to lower proviral load within peripheral blood CD4+ cells of infected mothers.