The objective of this study was to describe the natural history of HIV-1 RNA load in vertically HIV-1-infected children. HIV-1 RNA in 156 plasma or serum samples (1-14, median 4 from each child) from 32 vertically HIV-1-infected children was detected with the NASBA technique (Organon Teknika, The Netherlands). Twenty-one children were prospectively followed from birth, and 11 were identified and included at the age of 7-89 (median 61) months. The highest numbers of HIV-1 RNA copies were seen at 1.5-3 months of age. A quadratic curve model showed a reduction of HIV-1 RNA with increasing age up to approximately 8 years, and thereafter increasing numbers, p(age) = 0.002, p(age2) = 0.008. This pattern was not typical for individual children in whom a great variation in HIV-1 RNA numbers was seen over time. The interval from birth to the first HIV-1 RNA peak ranged from 1.5 months to more than 2 years. The HIV-1 RNA levels remained relatively high and fluctuating over the years in symptomatic as well as in long-term asymptomatic children. This makes HIV-1 RNA determination in children more difficult to use than in adults, as the only tool for prediction of disease progression and for initiation of therapy.