When human peripheral blood lymphocytes (PBL) are cultured with either concanavalin A (Con A)-treated or control autologous T lymphocytes, the mitogenic responses of the PBL co-cultured with Con A-treated cells are much lower. We have investigated the cell surface receptor changes during culture of T cells with and without mitogen in an attempt to explain this differential regulatory phenomenon. We present data here which show that human T cells cultured in complete medium alone gain helper cells with time. Con A-treated T cells are known to lose helper cells during culture. Erythrocyte rosette-purified T cells were cultured with or without Con A for 84 h and the numbers of cells with receptors for the Fc regions of either IgM (T mu) or IgG (T gamma) were enumerated daily. T mu cells have been associated with helper activity while T gamma cells have predominantly suppressor activity. Treatment with 10 micrograms/ml of Con A decreased T mu by approximately 50%. Untreated cells, however, showed significant increases in T mu (44 +/- 30.5% in twelve individuals). The great variance in T mu increases is due to the fact that individuals having higher initial T mu values showed smaller increases. These changes probably represent the gain or loss of receptors because total cell numbers did not change. There was no significant change in the number of T gamma cells in either control or Con A-treated cultures during the same 84 h period. In co-culture experiments in which the responses of fresh autologous PBL were determined, 60-h control T-cell cultures enhanced the mitogen responses of the fresh cells.(ABSTRACT TRUNCATED AT 250 WORDS)