Four individuals with increasing severity of HIV-1 infection were studied for serum neutralizing activity against their own virus isolates collected during 1-3 years. Sequential serum samples and HIV-1 isolates were available from these patients from the stage of lymphadenopathy to severe immunodeficiency. The replicative capacity of isolates changed from slow/low to rapid/high in each patient during the study period. Sequential virus isolates showed differences in sensitivity to neutralization by autologous as well heterologous area. Taken together with our previous results demonstrating that variant viruses resistant to neutralization by autologous sera emerge during the year following primary infection, neutralization-resistant variants seem to emerge during the entire course of HIV-1 infection. The ability to produce neutralizing antibodies to autologous virus appears to correlate with replicative capacity of the virus and the degree of immunodeficiency in the patient.