Guinea pigs with large intramuscular tumors showed impaired delayed cutaneous hypersensitivity to specific antigens and decreased skin inflammatory reactivity to nonspecific agents. Induced peritoneal exudates from these animals contained fewer cells than those obtained from tumor-free animals. The number of peripheral blood leukocytes in tumor-bearing animals was normal or increased, and the turnover rates for monocytes and polymorphonuclear leukocytes were increased. However, in vitro, lymphocytes from animals with tumors responded to antigen as measured by increased DNA synthesis and the production of skin reactive factor. The defect in skin reactivity may be due to an impairment of one or more factors related to immunologically nonspecific components of cell immunity.