Endotoxin (LPS) at sublethal doses injected i.v. into rats was found to induce IL-6 mRNA expression peaking at 1 to 2 h in whole organ RNA preparations of the spleen, liver, lung, bowel, and kidney. IL-6 serum protein levels also peaked at 2 h. TNF and IL-1, generally considered to be among the most rapidly released cytokines, also induced IL-6 expression. IL-6 in turn inhibited TNF and IL-1 expression, suggesting that IL-6 may be part of a negative feedback mechanism in the cytokine cascade. Dexamethasone down-regulated and Corynebacterium parvum up-regulated IL-6 expression, although the possibility cannot be excluded that these immunomodulating factors may in part have exerted their effects indirectly via the up- and down-regulation of TNF and IL-1. IL-6 injected i.v. at a pathophysiologically relevant dose caused a peripheral neutrophilia and mild myeloproliferative effect in the bone marrow.