Strains of Mycoplasma fermentans, isolated relatively recently from patients, induced a lethal toxicity in mice 24–48 hr after the ip injection of approximately 1010 cfu. Stock laboratory strains did not induce a lethal toxicity. Mice died of a syndrome that resembled shock and was similar to that caused by endotoxins of gram-negative organisms. Histopathologic changes provided evidence for overwhelming systemic infection and cellular necrosis without neurologic involvement. Toxic and control strains of M. fermentans were similar in morphologic, cultural, and biochemical properties. Hydrogen peroxide and arginine deiminase production did not correlate with toxigenicity. An exotoxin was not demonstrable. Viable organisms were recovered from the major organs and reached a peak concentration 6–8 hr after injection. Lethal toxicity appeared to be associated with a cell component of M. fermentans that killed mice when it reached sufficient concentrations in vivo.