OBJECTIVE: To study the susceptibility of primary HIV-1 isolates towards autologous and heterologous neutralizing antibodies (NAb). DESIGN: Blood was collected and primary HIV-1 isolated from individuals residing in Rio de Janeiro, Brazil, in all phases of disease. METHODS: Primary HIV-1 isolates were incubated with autologous or heterologous plasma and neutralization of infection of freshly pre-stimulated normal human peripheral blood mononuclear cells was assayed in parallel to median infectious dose determinations in the absence of antibodies. Levels of HIV-1 p24 antigen were used for evaluation of viral neutralization. RESULTS: Autologous neutralization (75%) was observed for 13 (52%) out of 25 of the primary HIV-1 isolates, and 15 (71%) out of 21 isolates were susceptible to 75% heterologous neutralization by at least one-half of the heterologous plasma tested. Primary HIV-1 isolates susceptible to autologous NAb showed a higher susceptibility towards neutralization by heterologous NAb than isolates that could not be neutralized by the autologous plasma (P = 0.049). The susceptibility of the primary HIV-1 isolates towards neutralization by heterologous NAb was significantly higher for isolates derived from men (P = 0.001), and for isolates obtained from individuals infected through homo-/bisexual risk behaviour in comparison with those infected through heterosexual HIV-1 transmission (P = 0.03). CONCLUSIONS: Susceptibility of primary HIV-1 isolates to autologous and heterologous neutralization was significantly correlated, indicating that escape mutants may become resistant not only to autologous but also to heterologous NAb.