We outline the mechanisms contributing to the human form of the Koch phenomenon, which we define as necrosis occurring within 24-48 h of injection of mycobacterial antigen into the skin of past or present tuberculosis patients. It is probable that tissue damage mediated in the same way occurs in the lesions themselves. We suggest that the necrosis is mediated in part by cytokines, particularly Tumour Necrosis Factor (TNF), and that this occurs for three reasons. First, Mycobacterium tuberculosis evokes an immunoregulatory abnormality characterised by raised agalactosyl IgG. This abnormality, also found in rheumatoid arthritis, Crohn's disease, and Erythema Nodosum Leprosum, seems to be associated with dysregulation of cytokine release. Secondly, M. tuberculosis itself triggers further cytokine release. Thirdly, the normally protective role of TNF is distorted by several interacting properties of components of M. tuberculosis, which render the cytokine toxic to the host tissues. The immunoregulatory abnormality may be susceptible to correction by immunotherapy.