A patient who developed an acute brainstem syndrome following Mycoplasma pneumoniae respiratory infection is reported. MRI showed changes consistent with brainstem demyelination. Clinical features and laboratory investigations support an immune mediated mechanism with no evidence of direction CNS invasion. On the basis of this case and a review of the literature, we postulate two mechanisms for the development of M. pneumoniae associated CNS disease: direct CNS invasion causing meningitis and an immune-mediated acute disseminated encephalomyelitis (ADEM). This has obvious therapeutic implications.