Objective: To investigate changes in the expression of complement receptor 2 (CR2) on B-cells from HIV-infected individuals. CR2 is the C3d/Epstein-Barr virus receptor and has been implicated in B-cell activation. Changes in its level of expression may therefore be associated with B-cell dysfunction.Design: Cross-sectional study of HIV-infected adults and age-matched control donors.Methods: The percentage expression and mean fluorescence intensity of CR2 (and three additional markers: CD19, CD69, and a standard antigen designation: HLA-DR) was measured on CD20 + B-cells using a two-color flow cytometric assay.Results: This study demonstrated a highly significant (P= 0.0001) decrease in the percentage co-expression of CR2 on CD20 + B-cells in HIV-infected individuals, compared with control donors. The mean percentage of CD20 + cells co-expressing CR2 was 71% (s.d., ± 15%) in the HIV-seropositive patients and 94% (s.d., ± 4%) in the control group. The pattern of CR2 expression in a number of the patients suggested a decrease in antigen density on the cells. Decreased expression of CR2 did not correlate with disease stage (asymptomatic, AIDS-related complex, or AIDS), nor with CD4 + T-cell percentage or absolute count, in the seropositive group.Conclusions: The evidence for a role for CR2 in B-cell activation suggests that its decreased expression, which we have demonstrated in HIV-seropositive individuals, may be associated with the B-cell dysfunction observed in HIV infection. Our finding that expression of this marker is decreased even in asymptomatic patients is consistent with reports of early B-cell defects in such individuals. Further investigation of this possible association may shed some light on both the increased incidence of bacterial infections in HIV-infected adults and children and their impaired responses to certain immunizations.