Knowledge of the pathogenesis of pneumonia due to Mycoplasma pneumoniae has been derived primarily from experimental infection of rodents. As part of an effort to establish a model with a closer resemblance to man, three seronegative, young, adult rhesus monkeys (Macaca mulatta) were inoculated with M. pneumoniae (10(7.4) cfu per animal) by oropharyngeal administration of coarse-particle aerosol. Five to six days after exposure of the animals, cultures obtained from the upper respiratory tract were positive for M. pneumoniae. Each animal subsequently developed a serologic response, as determined by complement fixation, complement-mediated killing, and tetrazolium-reduction inhibition techniques. Infection was subclinical, and serial chest roentgenograms failed to disclose pneumonia throughout the course of infection. Blood cell counts and titers of cold agglutinins remained unchanged. Althought M. pneumoniae was recovered from the upper respiratory tract of two monkeys for 50 days, there was no evidence of transmission of infection to cage-mate controls inoculated with broth.