SUMMARYA histochemically active population of macrophages has been demonstrated in the cellular infiltrate that occurs as an immunological response to skin allografts in mice. The proportion of these active cells was found to increase to a peak of 50% 10 days after the application of the graft. The time required to demonstrate particulate acid phosphatase activity in these macrophages was shown to decrease, up to and over the point of graft rejection. Concurrent studies of lysosomal proteolytic activity and lysosomal permeability have led to the conclusion that a buildup of cells having very active lysosomal enzymes in the infiltrate could be, in part, responsible for the rejection of the donor skin.