Skin grafts on specifically sensitized mice vary in histologic appearance. They show either: (1) no vascularization, and are usually referred to as white; (2) engorgement, hemorrhage, epithelial necrosis, and absence of lymphocytic infiltration; or (3) marked lymphocytic infiltration and a well preserved or hyperplastic epithelium. Because of their distinctive appearance in hematoxylin-eosin-stained sections, the hemorrhagic-necrotic type has been referred to by us as “red,” and the lymphocytic-hyperplastic type as “blue.” Blue grafts reflect a fairly weak, and red grafts a strong host response; white grafts reflect a particularly intense host response. The type of second-set grafts is determined by the immune response to the total number of donor antigens, which in turn is determined by the sum total of the histocompatibility differences between donor and host. Only theH-2locus is of sufficient strength by itself to elicit white grafts, but other loci in combination with each other can have the same effect. With immune responses of less intensity, there are fewer white and more red grafts, or fewer red and more blue grafts, respectively. Differences in allelic strength also are reflected in the white: red: blue ratio; a specific donor-host combination may result in predominantly blue grafts while reciprocal grafts are predominantly red. No data are available at present which would indicate that the variations in histologic appearance of second-set grafts result from differences in immune pathways.