Vitamin A deficiency maybe a risk factor for perinatal transmission of HIV-1 (Lancet. 1994;343:1593). Vitamin A enhances T-cell function and leukocyte phagocytic activity in vitro. Levels of vitamin A are decreased in newborns and infected HIV-1 pregnant mothers. Our hypothesis is that vitamin A may effect HIV-1 infection in cord blood lymphocytes and monocyte derived macrophages. We studied the effect of different concentrations of vitamin A and HIV-1 infection in cord blood lymphocytes and monocytes from 4 healthy(HIV negative) term infants. Lymphocytes and monocytes were isolated and cultured separately, then infected with HIV-1 (BAL strain). Supernatant was collected in triplicate on successive days for reverse transcriptase(RT) and p24 antigen analysis by radioimmunoassay and ELISA(Coulter, Miami, FL) respectively. Vitamin A significantly inhibited p24 viral replication by 50% at concentrations greater than 34.9 μmol/L in cord lymphocytes(101.1± 30.1 vs 219.4 ± 39.2, pg/ml, M±SD, p<0.0001, n=2) and 75% in monocytes(117.6 ±63.4 vs 507.0 ± 8.5 pg/ml p24, M±SD, p<0.025, n=2). Monocyte RT activity was decreased by 60%(3632± 1206 vs 9096 ± 1670 cpm/5μl, M±SEM, p<0.025, n=2). At concentrations less than 7.0 μmol/L p24 viral replication in lymphocytes was increased twofold(457.5 ± 77.2 vs 219.4 ± 39.2 pg/ml, M±SD, p<0.0001, n=2). In macrophages, RT was stimulated nearly threefold at concentrations less than 34.9 μmol/L (26078 ± 4757 vs 9096 ± 1670 cpm/5μl, M±SEM, p<0.025, n=2), but p24 antigen levels were unchanged. There was no cytotoxicity at 139.6 μmol/L. In summary, vitamin A significantly suppresses HIV-1 expression in both cord blood lymphocytes and macrophages at concentrations greater than 34.9μmol/L in a concentration dependent fashion. However, at concentrations less than 7.0 μmol/L vitamin A significantly stimulates viral replication. Thus, these observations may indicate that at high concentrations vitamin A may have the potential to inhibit HIV-1 replication in lymphocytes and monocytes in vivo and prevent perinatal transmission.