The utility of RNA virus load to predict progression of human immunodeficiency virus (HIV)-1 disease was assessed in 89 HIV-1-infected children. Of 22 virus load values during week 1 of life, 17 were below the detection threshold. Geometric mean virus load increased to approximately 7 x 10(5) copies/mL by week 4, was sustained throughout the first 6 months of life, and then declined to 1.6 x 10(5) copies/mL during the third year. Samples from week 1 of life had little predictive value, but virus load during days 7-30 strongly predicted progression to CDC-3 classification or death (P = .024; risk ratio = 1.6), and virus load during months 2-3 predicted progression to CDC-C or death within the first 6 months of life (P = .002, risk ratio = 11). Virus load was highly associated with imminent vulnerability to CDC-C or death (P = .002) during the first 18 months of life. Except for values from the first week of life, virus load at any age through 18 months is strongly associated with risk of HIV disease progression.