Lactoferrin (LF) is a mammalian iron-binding glycoprotein with antiviral effects. This preliminary study evaluated 6 months' LF (3 g/day, orally) treatment in 22 human immunodeficiency virus type 1 (HIV-1) vertically infected children. Plasma viral load and CD4+ cell counts were assessed every 3 months; before, during and after LF administration. No significant changes were observed during the pre-treatment period. By 6 months, mean (+/- SD) plasma viral load (log10) declined from 4.54 (+/- 0.65) to 4.28 (+/- 0.60); median percentage CD4+ cell count increased from 21.5% to 24.5%. Two months after treatment discontinuation, mean plasma viral load did not differ significantly from baseline or month 6 levels, but the percentage CD4+ cell count remained significantly higher than the baseline value. LF plus antiretroviral (ARV) therapy was more effective at increasing CD4+ cell count than LF alone. None of the patients showed any new HIV-1-related symptoms at follow-up. LF might be a useful addition to ARV therapy, but further large-scale studies are required.