Transfer factor preparations from 57 different donors have been compared for effects on mitogen- and antigen-induced lymphocyte transformation. Nine of the preparations were mitogenic when added to cultured lymphocytes although the magnitude of this activity was relatively low. The majority of the preparations (48/57) did not affect PHA-induced lymphocyte transformation although augmentation (6 of 57) and suppression (3 of 57) was observed with some. In addition we observed that most of the preparations tested suppressed ConA stimulation and augmented the PWM response. When selected preparations were evaluated on antigen-responsive cells, there was a correlation between the magnitude of antigen responsiveness and the magnitude of TF augmentation of antigen-induced lymphocyte transformation (p less than 0.005). Cultures that were not responsive to antigen (KLH-negative or BUdR-treated) could not be stimulated by TF from immune donors and antigen. These data suggest that TF preparations contain either stimulatory or inhibitory components and that TF is not capable of activating naive lymphocytes to undergo transformation in response to antigen.