Primary atypical pneumonia (PAP) was first described as a clinical entity distinct from bacterial and influenzal pneumonia in 1938.1 Central nervous system (CNS) complications, including meningoencephalitis, transverse myelitis, hemiplegia, ascending paralysis, and cranial nerve palsy were described in the initial and subsequent reports but little could be concluded about their pathogenesis since the etiology of PAP was unknown.2 In 1944, Eaton isolated a filterable agent from clinical cases of PAP and experimentally infected hamsters and cotton rats.3 It was a number of years, however, before the Eaton agent was generally recognized to be of etiologic significance. This occurred when Eaton agent isolates were visualized in chick-embryo lung tissue by immunofluorescent techniques and rises in fluorescent antibody titers were measured in the patients from whom the isolates were obtained.4,5 In 1962, the Eaton agent was cultured on artifical media, identified as a mycoplasma, and named Mycoplasma pneumoniae.6,7 With the subsequent general availability of cultural and specific serologie tech¬ niques, experimental studies in volun¬ teers and epidemiologie data con-firmed the etiologic role of M pneumoniae in many cases of PAP and defined its clinical spectrum.8-9Among individuals with culturally and/or serologically proved M pneu¬ moniae infection, 38 have been re¬ ported who have had CNS compli¬ cations. Fourteen were mentioned only incidentally, while 24 were de¬ scribed in sufficient detail to permit analysis.1023 It is the purpose of the present study to report four addi¬ tional cases of CNS disease associated with M pneumoniae infection and to review the previously reported cases in an attempt to characterize the clin¬ ical features and etiologic signifi¬ cance of this association.Patient Summaries Patient 1.-A 32-year-old housewife was in good health until four days prior to ad¬ mission when she developed a non¬ productive cough and low-grade fever. A roentgenogram of the chest showed a right upper lobe infiltrate for which she received antibiotics orally. One day prior to admis¬ sion, however, she developed high fever, severe frontal headache, nausea, vertigo, slurred speech, diplopia, and numbness of the right side of her face. She was admit¬ ted to another hospital where she was found to have a temperature of 102.6 F (39.2 C) and signs of meningitis. Cerebrospinal fluid (CSF) contained 191 leukocytes/cu mm; glucose, 64 mg/100 ml; pro¬ tein, 122 mg/100 ml; there were no organisms by smear or culture. She was given ampicillin trihydrate and penicillin G potassium parenterally and transferred to University Hospital, Columbus, Ohio, on Aug 8, 1969. There was no history of sore throat, ear ache, or myalgias in the recent past.On admission the patient was acutely ill. Her blood pressure was 96/60 mm Hg; pulse rate, 88 beats per minute; respira¬ tions, 28 per minute; and temperature, 100 F (37.8 C). She was lethargic with nuchal rigidity and had rales over the right ante¬ rior portion of the chest. Neurologic ex...