BACKGROUND: In infants and children with maternally acquired human immunodeficiency virus type 1 (HIV-1) infection, treatment with a single antiretroviral agent has limited efficacy. We evaluated the safety and efficacy of a three-drug regimen in a small group of maternally infected infants. METHODS: Zidovudine, didanosine, and nevirapine were administered in combination orally to eight infants 2 to 16 months of age. The efficacy of antiretroviral treatment was evaluated by serial measurements of plasma HIV-1 RNA, quantitative plasma cultures, and quantitative cultures of peripheral-blood mononuclear cells. RESULTS: The three-drug regimen was well tolerated, without clinically important adverse events. Within four weeks, there were reductions in plasma levels of HIV-1 RNA of at least 96 percent (1.5 log) in seven of the eight study patients. Over the 6-month study period, replication of HIV-1 was controlled in two infants who began therapy at 2 1/2 months of age. Plasma RNA levels were reduced by 0.5 to 1.5 log in five of the other six infants. CONCLUSIONS: Although further observations are needed, it appears that in infants with maternally acquired HIV-1 infection, combined treatment with zidovudine, didanosine, and nevirapine is well tolerated and has sustained efficacy against HIV-1.