AbstractWe assessed the effect of protein deprivation on the ability of peritoneal macrophages from Fischer rats to produce interieukin‐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 (δT6). Rats injected with IL‐1‐containing supernatants derived from peritoneal macrophage cultures of protein‐deprived rats had significantly less fever (δT6= 0.20 ± 0.09°) than rats injected with IL‐1 containing supernatants derived from peritoneal macrophage cultures of control rats (δT6= 0.56 ± 0.09°),P<.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.