The introduction of evoked response studies has disclosed the presence of asymptomatic lesions in multiple sclerosis (MS). This also raises an important question regarding the actual date of onset of the disease and the concept of disease activity. Close study of clinical exacerbations reveals that the recurrences of previously experienced symptoms are considerably more common than the appearance of new ones, and emphasizes the major role of physiologic and psychophysiologic alterations on the clinical course of the disease. The common practice of relating disease process activity to clinical symptoms is questioned in view of the nature of exacerbations and the poor anatomical correlation between demonstrable areas of activity revealed by radionuclide and contrast-enhanced CT scans and the patient's signs and symptoms. Symptomatic progression of MS may be due, in part, to relatively minor and subtle metabolic alterations of the interior millieu affecting the function of a nervous system with increased vulnerability.