Among human immunodeficiency virus-1 (HIV-1) vertically infected children, two patterns of disease progression have been observed: about 25% develop a severe immunodeficiency within the first 2 years of life; the rest experience a slower progression, like adults. We have assessed infectious viral burden in infected neonates through the French National Prospective Study. Plasma and cell-associated viremia were assayed by endpoint-dilution cultures in samples from 46 infants followed prospectively from birth. Plasma and cell-associated viral burden were found to be significantly higher in rapid progressing infants than in non-progressing infants in the first months of life: before the age of 2 months, between 2 and 4 months of age and by the age of 6 months. Moreover, among the non-progressing children, the infectious viral burden before the age of 4 months was predictive of the viral burden measured after the age of 12 months. In conclusion, this work demonstrates that infectious viral load is a reliable predictive marker for rapid progression to AIDS in infants and could be useful for initiating antiretroviral therapy.