SUMMARYC57BL/6J lymphoid cells incubated in vitro with C3H/He macrophage monolayers for a short time are capable of causing accelerated C3H skin graft rejection when transferred to syngeneic recipients. For C57 lymphoid cells to transfer this “sensitization,” certain requirements of the in vitro system must be met. (1) In vitro exposure to C3H macrophages must be maintained for at least 1 hr. (2) At least 15 × 106lymph node cells need to be transferred to syngeneic animals. (3) C57‐C3H cell contact is necessary for sensitization to occur. It was also found that (1) the in vitro sensitization reaction that causes subsequent accelerated graft rejection is specific for the strain used as macrophage source; (2) prolonged cultures of macrophages may contain a factor inhibiting the sensitization process; and (3) lymphoid cells from different sources vary in their ability to transfer this sensitization. Bone marrow and peripheral leukocytes are more efficient than lymph node and spleen; thymus cells are least efficient.