Summary The histologic picture of tuberculin skin tests in guinea pigs sensitized passively by the transfer of spleen and lymph node cells from BCG-immunized guinea pigs was investigated. As early as 90 min following intradermal injection of PPD numerous necrotic foci of muscle fibers and frequently also lipophagic foci were observed in subcutaneous tissue. Similar changes were not found in reactions to corresponding doses of ovalbumin given to the same animals and in tuberculin tests made in recipients of nonsensitized cells. Muscle fiber necroses occurred without demonstrable participation of inflammatory infiltration, which developed later together with the paresis of subcutaneous venules. These histologic findings are viewed as supporting the hypothesis that the reaction of hypersensitive cells with antigen leads to tissue damage, which in turn constitutes the principal cause of the development of inflammatory changes which form the second (nonspecific) part of the reaction.