We examined the neutralizing/enhancing activity in sera collected at an early and a later time point postinfection from 13 HIV-positive nonprogressors, 13 moderate progressors, and 13 rapid progressors to determine the relationship between neutralizing/enhancing activity and disease progression. Early sera from each group reduced virus replication at low dilutions (10-1 to 10-2) when compared with negative sera. The reduction was statistically significant for moderate and rapid progressors at 10-1 dilution (P = 0.02 and P = 0.02 respectively) but not for nonprogressors (P = 0.16). Late sera from nonprogressors and moderate progressors reduced virus replication at low dilution but late sera from rapid progressors lost neutralizing activity. These data suggest that an association exists between neutralizing activity in sera and nonprogression or slower progression to disease and that loss of neutralizing activity is associated with disease progression. At higher dilutions (10-3 to 10-6), both early and late sera from each group increased virus replication over negative sera. The levels and frequency of enhancement were higher for sera from a subgroup of nonprogressors than a subgroup of rapid progressors who exhibited enhancement. This suggests that enhancement is not associated with disease progression. The neutralizing/enhancing activity observed in sera of these three groups of subjects suggest that enhancement levels may reflect the overall level of antibody response to HIV. The replication patterns observed for early and late sera from individuals in the different groups reflect changes in antibody activity that appear to be associated with protection or disease progression. (C) 2000 Academic Press.