Previous studies have demonstrated that protein malnutrition adversely affects the synthesis and release of interleukin 1 by monocytic cells. The purpose of this study was to investigate the protein and trace metal metabolism of severely protein-malnourished guinea pigs given exogenous interleukin 1 in the postabsorptive state or while concomitantly receiving total parenteral nutrition (TPN). Protein-depleted guinea pigs in the postabsorptive state failed to exhibit fever, granulocytosis, accelerated amino acid oxidation, or an acute-phase protein response after administration of interleukin 1 or endotoxin. However, a reduction in the serum concentration of zinc (P less than 0.05) and iron (P less than 0.05) was observed in the guinea pigs given interleukin 1, but not in those given endotoxin. The short-term (1 day) administration of TPN restored positive leucine balance (P less than 0.001) and reduced leucine release from protein breakdown (P less than 0.001). No other differences in the protein metabolism or trace metal response to interleukin 1 were observed as a result of short-term TPN feeding. Body temperatures of these malnourished guinea pigs given interleukin 1 and TPN became febrile or hypothermic depending on initial body temperatures. It is concluded that an attenuated capacity to synthesize interleukin 1 and a failure to mount an appropriate acute-phase protein response to exogenously administered interleukin 1 exist in this protein-malnourished animal model. Furthermore, this diminished protein response appears to be independent of short-term substrate provision because TPN for 1 day was unable to restore the full effects of the acute-phase response as mediated by interleukin 1.