During the course of routine investigation of three isohistogenic strains of rats it was noted that sensitisation was more readily effected by allogeneic skin grafts than by the administration of dissociated allogeneic spleen cells. These differences were not entirely explicable in terms of either cell dosage, strain combination, the number of injections, the time between injection and challenge, or the route of inoculation. Possibly the large numbers of nonviable cells present in the spleen cell suspensions might have influenced the host response, and accordingly the effects of sensitisation with various nonviable inocula were investigated. Pretreatment of A strain recipients with large doses of killed allogeneic spleen cells prolonged skin graft survival times up to 21 times the normal mean time. The phenomenon was strain specific and was transferable by serum, although with some difficulty. Animals which had shown prolonged survival of their initial grafts usually showed prolonged survival of second grafts and sometimes also of third and fourth grafts. The skin graft rejection pattern in actively and passively conditioned recipients was characteristically different from that seen in untreated recipients, in that vigorous homograft reactions often subsided, allowing regrowth of donor strain hair. In contrast to the effects of pretreatment with killed inocula, administration of comparable untreated inocula usually gave rise to accelerated rejection of challenging skin grafts.