Na+- and K+-dependent adenosine triphosphatase [(Na+ + K+)-ATPase] was studied in microdissected samples from sections of histologically active and inactive plaques of multiple sclerosis. In active plaques the enzyme was found to be markedly reduced in activity, whereas in old, chronic plaques ATPase activities were higher than those of unaffected white matter. White matter from control patients and normal-appearing white matter from MS patients did not differ with regard to ATPase activities. The results suggest that reversible changes in the sodium pump mechanism may be involved in the pathophysiology of multiple sclerosis.