Substrate metabolism of skeletal muscle was studied by the forearm technique in eight patients with severe sepsis. The data were compared to those of 13 patients after elective surgery. In the septic group forearm blood flow was increased, but muscular utilisation of oxygen was diminished. Arterial concentrations of free fatty acids and ketone bodies were low. Thus, both only played a minor role in the supply of skeletal muscle with substrates. From the decreased production of lactate and alanine and the comparable utilisation of glucose we conclude that in the septic patients energy expenditure of skeletal muscle was mainly met by oxidation of glucose. In contrast to reduced lipolysis of adipose tissue intramuscular lipolysis may still be working since muscular production of lactate and glycerol was correlated. These findings suggest a changing pattern of arterial supply of substrates and utilisation of substrates by skeletal muscle during deterioration of clinical condition in the course of sepsis.