Treponema hyodysenteriae organisms, but not Treponema innocens, were capable of growing in the presence of fresh normal pig serum. A heat-labile component of the serum appeared to be responsible for the bactericidal activity since serum that was heat-inactivated for 30 minutes at 56(DEGREES)C was not bactericidal for T. innocens. The difference between T. hyodysenteriae and T. innocens in their susceptibility to serum components may be due to the outer envelopes of the treponemes;Lipopolysaccharide (LPS) extracted from T. hyodysenteriae was shown to be toxic for macrophages at concentrations of 15 (mu)g/ml and higher. Enhancements of Fc and C3 receptor-mediated phagocytosis by macrophages obtained from animals treated with treponemal LPS was noted. Treponemal LPS also induced the uptake of tritiated-thymidine by splenocytes and stimulated the generation of a chemotaxin in serum. The LPS was further implicated in the disease process caused by T. hyodysenteriae since the treponeme was able to cause lesions in LPS-susceptible, but not LPS-resistant strains of mice. Furthermore, the LPS was lethal for susceptible strains, but not for the resistant strains in the presence of actinomycin D. The treponemal LPS was chemotactic for macrophages from the LPS-resistant, but not the LPS-susceptible strains;The opsonic activity of serum from animals having recovered from infection with T. hyodysenteriae was shown to be serotype-specific. Because LPS extracted from the treponemes is the basis for serotyping, the results suggested that LPS may be important in protection of the host against T. hyodysenteriae.