The effects of recombinant interleukin-1 (IL-1), given as a continuous infusion for 6 days, on host responses were determined in rats. The development of fever, change in food intake and body weight, and key components of the acute-phase response in energy and protein metabolism were assessed. The effects of IL-1 were compared with those observed in a matched pair-fed group (semistarved), to distinguish the contribution from anorexia, and in a group that received IL-1 for 4 h acutely. IL-1 significantly increased core temperature, plasma levels of IL-6, and acute-phase protein production and decreased food intake and the circulating zinc level. The catabolic effects of IL-1 on nitrogen loss and muscle protein breakdown were independent of, and additive to those from malnutrition. The changes in energy expenditure, cumulative urinary nitrogen, and hydroxyproline excretion in the chronic IL-1 group were increased over semistarved animals. Finally, changes in muscle protein kinetics were only seen with chronic IL-1 infusion, and the changes in acute-phase protein were greater.