Traditionally, research in experimental allergic encephalomyelitis (EAE) has focussed on immunological and histopathological aspects. The present review introduces a physiological approach to EAE. As EAE is characterized by many small, focal lesions in the central nervous system (CNS), methods with a high spatial resolution should be used to conduct studies on regional pathophysiology in the condition. Quantitative autoradiography seems an ideal method as it offers, 1) high regional resolution (approximately 50 um), 2) precise quantitation and, 3) a direct correlation between regional histopathology and pathophysiology. By the use of this method, the author has performed studies on 1) regional blood-brain barrier (BBB) permeability, and 2) regional metabolism of energy substrate and related subjects, (i.e. regional cerebral blood flow, regional cerebral glucose metabolic rate and regional pH). Corresponding to the EAE lesions (lymphocytic accumulations), there is a considerable increase in BBB permeability. Metabolism of energy substrate at the lesion sites is severely deranged, which is expressed in a CBF/CMR ratio of 3 ml/mumol compared to the normal 1.5 ml/mumol. No changes in regional pH are seen in the lesions. Unrelated to the lesion sites there is a 50% decrease in blood flow in cerebral cortex. This observation probably reflects a functional decrease in cortical flow due to sensory motor impairment.