The effect of anaplastic carcinoma (15091A) and fibroblast cell culture supernates was examined in conjunction with Concanavalin A (Con A) on the splenic lymphocyte transformation of syngeneic A/J mice. Though both the tumor and normal cell culture supernates caused a dose-dependent suppression of the in vitro DNA synthesis of lymphocytes, larger depressive effects were observed with the former. Similar results were observed with supernates collected from tumor cell and fibroblast cultures in 10% heat inactivated fetal calf serum or serum-free media. The results of these experiments indicate that the depressed immunological reactivity observed in animals and human with cancer may be attributed to enhanced release of immunosuppressive factor(s) by malignant tissue into the body fluids of hosts.