The effect on muscle protein turnover of recombinant interleukin-1 alpha (rIL-1 alpha), 300 micrograms/kg body weight (BW) administered intraperitoneally (IP) in three divided doses over 18 hours, was studied in rats. Protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein, and total and myofibrillar protein breakdown rates were determined by measuring release of tyrosine and 3-methylhistidine, respectively, in incubated extensor digitorum longus muscles. To assess the role of glucocorticoids in rIL-1 alpha-related metabolic alterations, plasma levels of corticosterone following rIL-1 alpha injection and the effect of rIL-1 alpha on muscle protein breakdown in adrenalectomized and sham-adrenalectomized rats were determined. Total and myofibrillar protein breakdown rates were increased by 45% and 167%, respectively, following treatment of normal rats with rIL-1 alpha; muscle protein synthesis was not altered by the cytokine. Plasma corticosterone levels were markedly elevated following rIL-1 alpha injection, with a maximal level occurring at 30 minutes. However, administration of rIL-1 alpha resulted in increased total and myofibrillar protein breakdown rates in both adrenalectomized and sham-adrenalectomized rats. The results suggest that increased muscle proteolysis following administration of rIL-1 alpha is independent of glucocorticoids.