The role of neutralizing antibodies in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood and was assessed by evaluating responses at different stages of infection. Undiluted sera from long-term nonprogressors (LTNP) had broad neutralizing antibodies against heterologous primary isolates and were more likely to neutralize the contemporaneous autologous isolate than were sera from short-term nonprogressors and progressors. In primary infection, envelope-specific IgG was detected before the initial decline in plasma viremia, but neutralizing antibodies developed more slowly. Here, neutralizing antibodies against strains SF-2 and MN were sometimes the first to be detected, but titers were low for at least 17 weeks from onset of symptoms. Neutralizing antibodies against the early autologous isolate were detected for 4 patients by 5-40 weeks but were undetectable in 2 additional patients for 27-45 weeks. The results indicate that neutralizing antibody responses are slow to develop during primary infection and are uniquely broad in LTNP.