Anorexia and weight loss are serious complications that adversely effect the prognosis of cancer patients. It has been suggested that TNF/cachectin may cause cachexia. To determine if TNFlcachectin can induce progressive weight loss in tumor-bearing animals, a clone of the human TNF/cachectin gene was isolated and inserted into a mammalian expression vector. This construct was transfected into CHO cells, and a cell line (CHO/lNF-20) that secretes TNFlcachectin was isolated. A cell line (CHOICMV-Neo) that contains the same expression vector without the TNFlcachectin gene was also isolated. Nude mice injected intraperitoneally with CHOITNF-20 cells died more quickly than mice injected with CHOICMV-Neo cells. Eightyseven percent of mice inoculated intramuscularly with CHO/TNF-20 cells developed severe cachexia and weight loss. All mice bearing CHO/CMV-Neo tumors maintained or increased their body weight. We conclude that mice bearing tumors that secrete TNFlcachectin develop progressive wasting and die more quickly than mice bearing control tumors.