For each of 28 patients with RA and 27 normal controls, the in vitro lymphocyte responses to PHA and to Con A were simultaneously determined on aliquots of the same cell preparation. In the case of RA lymphocytes, the response to Con A was abnormally low when compared with the simultaneous response to PHA (P less than 0.01). Cells capable of responding to PHA were specifically killed with BUdR. The cells remaining after this procedure showed a relatively greater response to Con A than did the original population. In the case of RA lymphocytes, this relative increase in the response to Con A was significantly less than normal (0.02 greater than P greater than 0.01). These results suggest that a lymphocyte subpopulation, responding principally to Con A, is relatively reduced in RA.