In 23 patients with Mycoplasma pneumoniae (MP) infection (13 with pneumonia and 10 with an acute febrile, non-bacterial disorder of the central nervous system (CNS)) and in 26 healthy control persons, thymidine incorporation of blood lymphocytes stimulates stimulated in vitro by killed MP was studied. The lymphocyte response to MP was significantly higher in the pneumonia patients than in the controls. In the patients with an acute disorder of the CNS, lymphocyte responses to MP tended to be low or normal in lack of pleocytosis in the spinal fluid, but were predominantly high when either pleocytosis or a pulmonary infiltrate was present. Lymphocyte responses to the mitogens PHA, PWM and Con-A were normal in all groups. The lack of increased responses to MP antigen in some of the neurological patients, despite a current MP infection, may reflect an antigen-specific depression or a lack of specific sensitization of their lymphocytes.