It has been proposed that immunoregulatory cytokines play a role in the onset and development of cancer cachexia, although evidence supporting this theory remains inconclusive. In the present study, SCID mice were implanted with one of two tumor cell lines known to induce weight loss in rats. Growth of the Morris 7777 hepatoma was associated with weight loss as well as increased levels of tumor necrosis factor and interleukins 1 and 6 in spleen cells of tumor-bearing mice. Growth of the MCA sarcoma did not induce weight loss, nor did it increase cytokine expression in spleen cells of tumor-bearing mice. We conclude that increased cytokine expression is associated with weight loss in tumor-bearing SCID mice, and immune activation for cytokine expression does not require the presence of T or B cells.