Human immunodeficiency virus type 2 (HIV-2) has been reported to be less pathogenic than HIV-1. We have investigated the capacity of sera from nine HIV-2-infected individuals to neutralize their own autologous virus. All nine HIV-2-infected individuals neutralized autologous virus with titers ranging between 20 and 320. In contrast, we have previously reported that most HIV-1-infected individuals lack such antibodies. The difference between HIV-1 and HIV-2 infection was statistically significant (P < 0.0002, Pearson test) and the difference in neutralizing antibody prevalence may explain the faster disease progression in HIV-1-infected individuals than in HIV-2-infected individuals.