The sequence of events in homograft rejection of skin in mice was studied by light microscopy in comparison to the reactions to isografts. Male C3H mice were used as donors and Balb/c mice were the recipients. In non-infected grafts no invasion of graft tissue by inflammatory cells occurred except for the marginal areas bordering on the graft bed. The most constant feature of immunological rejection was occlusion of blood vessels at the graft-host border with ischaemia of the graft. This indicated that skin homograft rejection is mainly a vascular phenomenon which can be best diagnosed by the presence of empty venules and capillaries. Leukocytic infiltration was prominent in presumably infected grafts. Destruction and inflammatory infiltration of the epidermis was not found to be a criterion for immunological rejection. In the graft bed adjoining the graft the granulation tissue contained basophilic and small lymphocytes, and macrophages. These cell tended to concentrate nearest to the graft and were surrounded on the outside by the lymphoid cells. It is probable that the macrophages were active in digestion of breakdown products.