Cells obtained from the peripheral blood of HIV-infected patients and volunteers immunized with HIV-1 vaccines are commonly used to study anti-viral responses, since lymphocytes from the central lymphoid organs are difficult to obtain. Analyses involvingPBMCimplicitly assume that circulatingBcells provide an accurate reflection of the systemic humoral response induced by the HIV antigens. We examined this assumption by comparing the number ofBcells secreting IgG anti-gp160/120 antibodies in the peripheral circulation with serum antibody titers. Results indicate that neither the magnitude nor duration of the serologic response detected in HIV-infected patients or gp160/gp120-immunized volunteers reproducibly correlates with the number ofBcells secreting anti-envelope antibodies in the blood.