Ehrlichia risticii is a gram-negative obligate intracellular bacterium which primarily infects macrophages and crypt epithelial cells in the intestinal wall and is the etiologic agent of Potomac horse fever. To understand the pathogenesis of the disease, we tested whether E. risticii induces inflammation-associated products in thioglycolate-induced mouse peritoneal macrophages. Mouse peritoneal macrophages produced larger amounts of interleukin-la (IL-la) but lower levels of tumor necrosis factor alpha (TNF-a), IL-6, and prostaglandin E2 (PGE2) when exposed to live or killed E. risticii than when exposed to Escherichia coli lipopolysaccharide (LPS). Preincubation of macrophages with live or killed E. risticii suppressed TNF-a, IL-6, and PGE2 generation but not IL-la production in response to LPS. Murine gamma interferon treatment of macrophages did not influence TNF-a, IL-la, IL-6, or PGE2 production regardless of exposure to E. risticii. Intracellular cyclic AMP was significantly greater in E. risticii-infected macrophages than in uninfected macrophages. These results suggest that increased levels of IL-la but not TNF-a or PGE2 production by macrophages may be primarily involved in the pathogenesis of the disease caused by E. risticii. Increased intracellular concentration of cyclic AMP in infected macrophages may be chiefly responsible for the high level of IL-la and inhibition of TNF-a production in response to LPS. concentration of 106 cells/ml in RPMI 1640 (GIBCO)-10% FBS-2 mM L-glu-1% antibiotics (10,000 U of penicillin G sodium, 10,000 ,ug of streptomycin sulfate, and 25 ,ug of amphotericin B [GIBCO] per ml) and incubated at 37°C for 24 h in 5% C02-air. The medium and floating cells were removed, and the macrophages were washed twice with sterile phosphate-buffered saline (2 mM KH2PO4, 6 mM Na2HPO4, 2 mM KCl, 136 mM NaCl). Then, DH82 lysate, 4333 on July 16, 2020 by guest . 1989. Tumor necrosis factor alpha is a cytotoxin induced by murine Chlamydia trachomatis infection.