Supernatants of mouse lymphocyte cultures briefly exposed to phytomitogens or various antigens may contain factors---lymphokines--which are mitogenic for lymphocytes in the absence of any additional stimulatory agents. Whether such supernatants can modulate the proliferative responses of lymphocytes exposed to phytomitogens or allogeneic cells is the subject of the present investigation. Active supernatants were obtained from cultures of either mouse lymph node cells incubated with concanavalin A bound to Sepharose or allogeneic cells for 24 h. Both types of active supernatants reduced the 3H-thymidine uptakes of lymph node cells and cortisone-resistant--medullary--thymocytes in response to various phytomitogens and allogeneic cells. In contrast, normal suspensions of mouse thymocytes, containing both cortical and medullary lymphocytes, exhibited stimulations higher than anticipated. The results indicate that activated lymphocytes may release factors which reduce proliferative responses of some lymphocytes, presumably immunologically mature T cells, and enhance the responses of other lymphocytes which are relatively immature.