Peripheral T lymphocytes are self-renewable cell populations since, when transferred into syngeneic T cell-deficient athymic mice, they expand in the absence of exogenous antigen stimulation. Quantification of the expansion potential of CD4+ cells by transfer of the same population into successive host mice shows that these cells are able to divide up to 56 times in vivo. Therefore, as a population, CD4+ cells can increase in size 8 x 10(5)-fold, an expansion potential of similar magnitude to that previously reported for colony-forming units. Injection of different numbers of T cells at different CD4/CD8 ratios is followed by T cell accumulation to a similar plateau in recipient nude mice. This indicates that peripheral T lymphocytes are tightly regulated by homeostatic mechanisms that control pool sizes and CD4/CD8 ratios, in a manner independent of the cell input into the peripheral compartment. This kinetic behavior of mature T cells permits the maintenance at the periphery of any T cell specificity previously selected in the thymus. The expansion capacity of peripheral T cells may also allow extensive modulation of peripheral T cell specificities, which would confer a major role to post-thymic selection of mature peripheral T cell repertoires.