Biological activities of lipopolysaccharide-like (LPS-like, phenol/water extract) and endotoxin-like (butanol/water extract) preparations from Trepomena hyodysenteriae were examined. The treponemal phenol/water and butanol/water extracts were less toxic than E. coli LPS for murine peritoneal exudate cells (PECs). The treponemal phenol/water extract did not stimulate the production of interleukin-1 (IL-1) or tumor necrosis factor (TNF) from murine PECs. The treponemal butanol/water extract did induce production of IL-1 and TNF but at doses 5- to 50-fold higher than E. coli LPS. Natural killer cell activity was augmented by the treponemal butanol/water extract but not by the phenol/water extract. Suppression of a splenic anti-SRBC plaque forming cell response was observed when the LPS-like and endotoxin-like preparations from T. hyodysenteriae were administered 24 h prior to injection of the SRBC. These findings indicate that the butanol/water extracted material from T. hyodysenteriae is more biologically active than the phenol/water extracted material and that the treponemal endotoxin may contribute to the inflammatory response of swine dysentery by inducing IL-1 and TNF production.