We assessed the effect of protein deprivation on the ability of peritoneal macrophages from Fischer rats to produce interleukin-1 (IL-1) after in vitro stimulation. Pyrogenic activity of supernatants was measured by an in vivo febrile response assay. Control rats were given a 23% casein diet and protein-malnourished rats were given an 8% casein diet for 4 weeks. IL-1-containing supernatants prepared from peritoneal macrophages were injected into assay rats, whose temperatures were measured for 6 hours (delta T6). Rats injected with IL-1-containing supernatants derived from peritoneal macrophage cultures of protein-deprived rats had significantly less fever (delta T6 = 0.20 +/- 0.09 degree C) than rats injected with IL-1 containing supernatants derived from peritoneal macrophage cultures of control rats (delta T6 = 0.56 +/- 0.09 degree C), P less than .01. Protein malnutrition leads to diminished pyrogenicity of macrophage culture supernatants and may be at least partly responsible for the decreased febrile response seen in the malnourished animals.