HIV is known to be present in massive amounts in both resting and actively replicating cells in infected individuals. We tested the combination of didanosine and hydroxyurea, known to suppress viral production in vitro in both of these cell types, in a small number of asymptomatic patients. After 3 months of well tolerated treatment, we observed a large reduction of viral load in the peripheral blood of all 12 patients, down to nonquantifiable levels in 7 of 12 as measured by infectious virus titer, and 6 of 12 as measured by plasma HIV-RNA. In this subgroup of 6 patients, whose baseline HIV-RNA was below 14,000 copies/ml, the median increase in CD4+ count after 90 days of treatment was 244 cells/mm3.