Reclustering and indirect immunofluorescence assays on MT-4 cells [carrying both CD4 and complement receptor type 2 (CR2)] were used to measure neutralizing and enhancing antibodies in sera obtained from HIV-1-infected individuals. Heat-inactivated sera were tested before and after mixing 1:1 with fresh seronegative human serum. Using heated samples, neutralizing antibodies were found in 20 out of 20 and 11 out of 19 serum samples of asymptomatic and symptomatic [AIDS, AIDS-related complex (ARC)] HIV-seropositive patients, respectively. In complement-restored samples, neutralizing activity was found in eight sera of asymptomatic patients and in none of the sera of AIDS and ARC patients; enhancing activity could be detected in four and 12 sera, respectively. A significant positive correlation was observed between the titres of neutralizing antibodies measured in the complement-restored samples and the absolute number of CD4+ lymphocytes. These findings indicate that the appearance of complement-dependent enhancing antibodies coincident with the loss of neutralizing antibodies may indicate a poor prognosis in HIV infection.