Previous reports have failed to demonstrate integumentary allograft rejection in insects. We realized however, that these studies may not have fully appreciated the structure of the insect exoskeleton. Since the sub-cuticlar epidermal layer constitutes the only living tissue associated with insect integument, its destruction would indicate that the animal recognized and responded to the foreign tissue. Thus, we investigated allograft reactivity in the American cockroach, Peripla-neta americana, by observing the fate of the epidermal portion of the integument. Each animal in a pair received a 3x4-mm integumentary allograft from its partner, as well as a 3x4-mm control autograft. The transplants were then examined histologically for signs of epidermal destruction at 0, 1, 3, 5, 7, and 10—70 days (in 10-day increments) posttransplantation. The results indicated that significant rejection of the allografts began by day 3, with peak reactivity occurring by day 7 when 92% of the grafts were scored as rejected. At later periods (>20 days), the graft sites showed signs of re-population by host epidermal cells. The allograft reaction was found to lag behind the xenograft reaction, which showed peak activity after only 1 day posttransplantation. Even so, allograft rejection in this insect occurred quite rapidly (as compared with some other invertebrates), and would appear to be due to a cytotoxic reaction against the epidermal layer. © 1987 by The Williams and Wilkins Co.