To investigate age-related alterations in human humoral immunity, we analyzed the quantity and quality of peripheral B cell subsets, CD27-negative (CD27⁻) and CD27-positive (CD27⁺) B cells, by flow cytometry analysis in 54 aged individuals (mean age ± SE, 74.6 ± 0.7 years) and 30 young individuals (mean age ± SE, 26.1 ± 0.5 years). CD27⁻ and CD27⁺ B cells are regarded as naive and memory B cells, respectively. CD38, Ki-67, CD95 and bcl-2 were used as activation, proliferation and apoptotic markers. Susceptibility to apoptosis was evaluated by cell size and annexin-V binding in culture cells. The percentage of CD27⁺ B cells was significantly lower in aged (mean, 19.2%) individuals than that in young individuals (mean, 28.2%). The opposite was true for CD27⁻ B cells (mean, 80.8% in aged and 71.8% in young) (P < 0.01). The absolute number of CD27⁺ B cells in aged individuals was significantly less than the number of CD27⁻ B cells. The CD27⁺ B cells from aged individuals showed little susceptibility to apoptosis, although CD95 expression on the CD27⁺ B cells was significantly higher in the aged individuals than in the young individuals (P < 0.05). The CD38 and bcl-2 expression on the CD27⁻ B cells was significantly higher in the aged individuals than in the young individuals (P < 0.05). In addition, the CD27⁻ B cells from the aged individuals showed a decreased susceptibility to apoptosis compared with that of the young individuals. These findings suggested that human aging leads to both quantitative and qualitative alterations in the peripheral B cell developmental system, including memory and naive B cell balance and their surface phenotypes.