The lipid A component of bacterial lipopolysaccharides (endotoxins), when complexed to bovine serum albumin (BSA) or human serum albumin (HSA), was shown to be a potent pyrogen. Furthermore, rabbits could be protected against endotoxin fever by immunization with both lipid A.BSA and lipid A.HSA complexes. The results presented in this paper show that lipid A is responsible for the pyrogenic activity of endotoxins and their ability to induce pyrogenic immunity.