Diverse pathological states (sepsis, trauma, neoplasia) cause widespread and profound alterations of metabolism (Forse and Kinney, Surgical infection in critical care medicine, pp. 69-94, Edited by Meakins, Churchill Livingstone, 1985). Such changes occur peripherally (muscle, adipose tissue) and centrally (liver); while peripheral metabolic changes are almost exclusively catabolic, hepatic changes are more complex and poorly understood. Thus in contrast to the net protein catabolism in muscle in stress states, there is an increase in the synthesis and secretion of specific hepatic proteins, the so-called phase (e.g., C-reactive protein, armacroglobulin, serum amyloid A), whereas the synthesis of other proteins (albumin, transferrin) by the liver is decreased (Heinrich et al., Biochem. J. 265, 621-636, 1990). The general view is that peripheral protein is used to provide a source of amino acids for gluconeogenesis and for the synthesis of the acute phase proteins, whose physiological function is uncertain. Sepsis and neoplasia are also associated with HTG and the aim of this contribution is to discuss this phenomenon. The HTG could be due to decreased utilization of triacylglycerols resulting from decreased activity of lipoprotein lipase in muscle and (or) adipose tissue, or increased secretion of VLDL by the liver. There are two sources of fatty acid for VLDL synthesis: increased flux of fatty acid to the liver due to stimulation of lipolysis in adipose tissue or increased de novo synthesis of fatty acids within the liver. In addition, decreased hepatic oxidation of fatty acids may lead to their greater availability for secretion as VLDL. In this connection there is evidence for decreased ketone body formation and hypoketonaemia in sepsis (Beisel and Wannemacher, J. Parent. Ent. Nutr., 4, 277-285, 1980). Irrespective of the mechanisms for the genesis of the HTG, there are two further questions: (i) the nature of the signal(s) that cause the changes in tissue lipid metabolism and (ii) what, if any, is the function of the HTG? The mechanisms for HTG discussed above have been examined in septic humans and in experimental animal models of systemic infection. Lipoprotein lipase activity is decreased in both white adipose tissue and skeletal muscle of septic patients with HTG (Robin et al., Surgery, 90, 401-407, 1981) and there is evidence for increased lipolysis and fatty acid turnover (Forse and Kinney, op. cit.). Paradoxically, in view of the peripheral changes, hepatic lipogenesis is increased during septicaemia in the rat following Escherichia coli infection and there is decreased