1. Data are presented demonstrating in sublethally x-irradiated (670 rad) mice the differential radiosensitivity of the first and second-set responses to allogenic (H-2 difference) and xenogenic (rat) skin grafts. The second-set response is more radioresistant than is the first-set response; the second-set response to a xenogenic skin graft is more radioresistant than is that to an allogenic graft; the converse is true with regard to the first set response.

  2. The “homograft sensitivity” induced with xenogenic or allogenic dissociated skin or spleen cells (with the methods used) appears to be “inferior” to or unlike that induced with skin grafts. Sensitization with xenogenic dissociated cells resulted in a more vigorous response (i.e., shorter rejection time) to subsequent appropriate grafts in both nonirradiated and sublethally irradiated mice than did sensitization with comparable allogenic tissues.

  3. Allogenic skin grafts survived significantly longer on sublethally irradiated mice, presensitized with allogenic dissociated spleen cells than they did on the appropriate controls. By contrast, presensitization with allogenic dissociated skin cells had essentially no effect on allogenic graft survival in sublethally irradiated mice.

  4. Nonirradiated and sublethally irradiated (670 rad) mice previously sensitized with rat skin grafts rejected subsequent first-set allogenic grafts significantly sooner than did their appropriate controls. This effect was not seen when the mice had been previously sensitized with dissociated rat skin or spleen cells.

  5. Neither the initial method of sensitization nor sublethal irradiation influenced the sensitization induced by subsequent skin grafts.

  6. Certain observations made during the accelerated rejection of allogenic and particularly of xenogenic skin grafts suggested either the presence of a nonspecific agent capable of disrupting the capillary bed at the graft sites or the deficiency of a factor essential to the maintenance of capillary wall integrity.

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