Mycoplasma pneumoniae represents one of the most common etiologic agents of lower respiratory tract disease of man. Data from a 12-yr period of surveillance in Seattle, WA, USA, revealed that infection rates varied from 2% in endemic years to 35% in epidemic periods (J Infect Dis 139: 681, 1979). Most persons with M. pneumoniae infections have a relatively mild disease, which is not usually accompanied by frequent complications. Atypical pneumonia caused by the organisms is most prevalent in school-age children, with peak occurrence at about 10 years old. In this group, 13 to 18% of those infected develop pneumonia. Clinical disease is uncommon below 4 and above 50 years of age. M. pneumoniae infections probably occur throughout the world. It has been estimated that approximately 50% of the infections in adults but only 20% in children are completely asymptomatic. The usual clinical picture of atypical pneumonia and the wide range of unusual manifestations of M. pneumoniae disease are presented. Except for a few single case reports, histopathology of M. pneumoniae disease has been extensively studied after experimental infection of hamsters and guinea pigs. These animal models had to be developed because of the benign course of most M. Pneumoniae diseases in man. Due to this limited information on the pathology of natural disease, comments on its pathogenesis are also based on findings using experimental models. Infection is established by attachment of the organisms to the surface membrane of ciliated epithelial cells. Antigenic similarities between the glycolipids of M. pneumoniae membranes and host tissue, unspecific blastogenesis and immunosuppression during infection have been described. These phenomena may explain a decreased protective immune mechanism of the host during infection. Several as yet unexplained features of M. pneumoniae disease support the hypothesis that lung infiltrates in M. pneumoniae infection may be, in part, immunologically determined in a host sensitized by one or more silent infections.