Treatment of human immunodeficiency virus (HIV) infection with nevirapine in patients with < 400 CD4 cells/mm3 rapidly selects for virus with reduced susceptibility to nevirapine. To test whether resistance would develop less quickly in patients with a lower virus burden, nevirapine was studied in asymptomatic patients with > 500 CD4 cells/mm3. With 400 mg of nevirapine daily, the median reduction in HIV RNA was 0.51 log10 copies/mL, and all isolates recovered by 12 weeks were resistant to nevirapine. As in patients with lower CD4 cell counts, some patients experienced sustained reduction in plasma HIV RNA despite the presence of resistant virus. These results suggest that lower levels of HIV RNA and immunosuppression did not retard the rate of emergence of nevirapine-resistant virus; also, a polymerase chain reaction-based HIV RNA assay is sufficiently sensitive to evaluate the antiviral effect of a drug in patients with > 500 CD4 cells/mm3.