So far, there has been a tendency towards a uniform concept of the role and kinetics of TNF and other cytokines in septic shock. However, our comparison of data from different groups of shock patients clearly demonstrates marked differences. On the one hand, the cytokine pattern in experimental septic shock and meningococcal disease has similarities which include early burst releases of TNF and IL-6. On the other hand, intensive care unit patients which includes patients with polytrauma, surgery, burns and other underlying diseases have a completely different pattern of appearance of TNF and IL-6 in the circulation. We have not been able to detect bioactive TNF in the circulation of these patients, whereas others have measured elevated levels of immunoreactive TNF. Bioactive IL-6 can be detected in serum; however, the levels are often fluctuating and there is no common pattern of appearance. These differences probably reflect differences in the release of endotoxin and the immunological status of the patients. TNF inhibitors and soluble TNF receptors probably play an important role. Experimental models for septic shock most commonly use administration of live bacteria or endotoxin to anesthesized healthy animals. This appears to be a good model for meningococcal disease, but not for intensive care unit patients.