The diagnosis of multiple sclerosis (MS) is clinical and verifiable at post mortem. Neuropathological examination of 518 consecutive patients with clinically definite MS revealed a correct diagnosis in 485 cases (94%). Clinical diagnosis had been established by a neurologist in all cases. Erroneous diagnosis included a variety of other neurological disorders. Also investigated was a randomly selected series of 33 patients with a clinical diagnosis of probable MS: post mortem confirmation of MS was obtained in circa 66%, for the remainder the error pattern was similar to the above. Clinical diagnosis of definite MS was correct in 94% cases. Laboratory tests and examinations have not radically improved diagnosis. Neuropathological examination may occasionally fail to demonstrate MS plaques if the optic nerves are not investigated.