B lymphoblasts immortalized by the Epstein-Barr virus (EBV) exhibit autocrine growth stimulation--that is they release a soluble activity to which they respond by growth. A minimally supplemented serum-free medium conditioned by lymphoblastoid cells in their log phase of growth (LCL-CM) was found to contain autostimulatory activity allowing us to explore the mechanism of autocrine growth for these cell-types in defined conditions. Below cell densities capable of supporting autonomous growth, continued proliferation in serum-free medium was dependent on both added LCL-CM and transferrin. Neither activity alone was capable of sustaining growth. At higher cell densities, transferrin by itself was sufficient to maintain the autocrine loop. The action of the autostimulatory factor appeared to reside in its ability to prime cells continually for a proliferative response to transferrin by enhancing the expression of transferrin receptors at the lymphoblast surfaces. The implications of these findings for normal B cell physiology and their possible relation to oncogenesis are discussed.