Four silvered leaf monkeys inoculated with Mycoplasma fermentans (incognitus strain) showed wasting syndromes and died in 7-9 months. Infected animals had a late and transient antibody response to mycoplasmal infection. Three monkeys revealed periodic mycoplasmal antigenemia. The one that had the most persistent antigenemia failed to mount a detectable antibody response and was the first to die of the infection. The control monkey was killed 8 months later, after the last of the infected animals had died, and revealed no evidence of seroconversion or antigenemia. Polymerase chain reaction, immunohistochemical, and electron microscopic studies identified systemic infections of M. fermentans in the infected animals. No other opportunistic infection or neoplastic disease was found. It is interesting to note the absence of an inflammatory reaction to the large number of mycoplasmas in the infected tissues. M. fermentans (incognitus strain) apparently suppressed normal inflammatory or immune responses, produced wasting syndromes, and caused a fatal systemic infection in these monkeys.