Brainstem and cortical Lewy bodies in diffuse Lewy body disease show intense immunoreactivity to antibodies against ubiquitin. Quantitative studies show that the novel neuropathological technique of anti-ubiquitin immunocytochemistry is more than twice as sensitive as conventional haematoxylin and eosin stains in detecting cortical Lewy bodies. Anti-ubiquitin immunocytochemistry should be regarded as the method of choice for the diagnosis and quantification of diffuse Lewy body disease.