The B cell responsiveness mediated by T cells has been evaluated in 50 aged donors by using a Pokeweed mitogen (PWM)-driven differentiation system. Peripheral blood mononuclear cells (PBMC) from aged donors exhibited a lower plaque-forming cell (PFC) generation in comparison with young donors. Similar results were obtained by using, on a per cell basis, purified T cells supplemented with Non-T lymphocytes. OKT4+ cell addition to Non-T cells enhanced PFC number, even if values were still lower when compared to young donors. Moreover, results similar to those seen with T-supplemented Non-T cell cultures were obtained by mixing Non-T cells with OKT4+ and OKT8+ lymphocytes. Interestingly, when OKT8+ cells were divided into OKT8+M1+ and OKT8+M1-subsets and used in the assay, both cell fractions suppressed B cell response in aged donors, while this effect was mediated by OKT8+M1+ cells only in the young counterpart. Soluble suppressive factors were responsible for the observed activity, since indomethacin supplementation to cultures or overnight incubation of cells before PWM stimulation abrogated the OKT8+M1--mediated suppression. Taken together, these findings suggest an additional alteration of T-B cell relationship in the elderly.