The clinical applicability of the revised McDonald diagnostic criteria of primary progressive multiple sclerosis (PPMS) was assessed in 17 patients with a longstanding PPMS diagnosis (mean 15 years). All patients were re-evaluated with clinical examinations, magnetic resonance imaging (MRI) of the brain and the spinal cord, extensive laboratory tests, and 12 patients underwent cerebrospinal fluid (CSF) examination. No diagnosis more likely than PPMS was disclosed. All patients had brain and spinal cord lesions on MRI. In 15 patients the brain lesions and in 14 the spinal cord lesions fulfilled the revised McDonald criteria for positive scans. No contrast-enhancing lesion was observed despite administration of triple doses of gadolinium. In total, 12 patients fulfilled the revised McDonald MRI criteria for PPMS. Of the remaining five patients who incompletely fulfilled the revised MRI criteria, all had CSF findings supporting the diagnosis PPMS. Thus, CSF analysis was required in addition to MRI in about one-third of the patients to establish the diagnosis of PPMS.