Erythroid stem cell proliferation is regulated by lymphokines and erythropoietin. The helper subset of T lymphocytes is known to produce the erythroid growth factor IL-3 or burst-promoting activity (BPA), while the suppressor subset seems to inhibit the erythroid growth. Leukocyte-conditioned media derived from white cells of nonanemic elderly were reported to provide defective support to the erythropoiesis. In two groups of elderly, nonanemic and anemic, we studied the ability of T lymphocytes to stimulate the BFU-E growth and the in vitro effect of cimetidine, as a drug that inhibits the suppressor T lymphocytes. Culture data were then compared with the peripheral blood lymphocyte picture. The study shows that defective mononuclear cell support to the BFU-E growth, namely due to reduced absolute number of the T4 subset of T lymphocytes, can be observed in both anemic and nonanemic elderly. It is suggested that isolated defective BPA production is not always sufficient to induce anemia. In most cases, anemia of unexplained origin in senescence would be due to the concomitance of both BFU-E impairment and defective BPA production. The simultaneous evaluation of BFU-E growth, lymphokine production, and the T-lymphocyte blood picture offers the best way to investigate the erythropoiesis of the elderly.