Experimental work in animal models is providing important clues on the specific function of tumor necrosis factor (TNF) and its receptors in disease, especially on the molecular and cellular pathways through which TNF mediates beneficial and deleterious responses. Emerging data on the posttranscriptional regulatory processes, secretion, and postreceptor actions of TNF indicate a variety of mechanisms that may be causative of disease. More recent evidence in murine disease models has indicated heterogeneity of TNF receptor usage in autoimmune disease suppression versus inflammatory tissue damage, suggesting that selective TNF receptor inhibition may be advantageous to anti-TNF treatments in combating chronic inflammatory disease.