There is evidence that both counter-regulatory hormones, in particular glucocorticoids, and cytokines influence amino acid and protein metabolism in skeletal muscle, and that these two groups of regulators interact in the development of muscle catabolism. Glucocorticoids stimulate muscle proteolysis during sepsis and also in other catabolic conditions. In addition, glucocorticoids regulate muscle glutamine metabolism, resulting in increased glutamine release and reduced glutamine concentrations in skeletal muscle. Glucocorticoids inhibit the glutamine transporter in skeletal muscle and stimulate glutamine synthetase activity. Proinflammatory cytokines, in particular tumor necrosis factor and interleukin-1, inhibit muscle amino acid transport by system A, and these cytokine effects are probably indirect. Most of the catabolic effects of tumor necrosis factor in skeletal muscle, including stimulated protein degradation and inhibited amino acid uptake, are mediated by glucocorticoids.