The secondary response of human lymphocytes following restimulation with alloantigens has been studied. If fresh stimulating cells are added to a mixed leukocyte culture (MLC) at a time when the peak of proliferative and cytotoxic activity has passed, a rapid reactivation occurs. The secondary response in MLC demonstrates specificity such that restimulation with the original sensitizing cell (or one presumably sharing the LD genetic determinants responsible for triggering MLC) induces a greater proliferative response than a third-party cell. On the other hand, the secondary cytotoxic response is directed towards the SD antigens of the original sensitizing cell regardless of which cell is used for restimulation. Possible mechanisms of cellular interactions are considered to explain these results.