Clinical and laboratory studies are conducted to determine etiology (infection, immunity and/or genetics) of chronic diseases of the neuromuscular system and design effective therapies. Current studies involve patients with polymyositis/dermatomyositis (PM/DM), post-polio syndrome, amyotrophic lateral sclerosis (ALS), demyelinating polyneuropathies, neuromuscular diseases associated with HIV infection, and hypokalemic periodic paralysis. The pathogenesis of post-polio syndrome is explored with a series of electrophysiologic, virologic, immunologic and histologic studies. The findings are compared with those seen in patients with acute paralytic poliomyelitis and other motor neuron diseases. Persistent or mutant poliovirus is sought in these patients' tissues using tissue cultures, polymerase chain reaction (PCR), and in situ hybridization. Because abnormal immunoregulation was found in some patients, a double-blind placebo-controlled trial using prednisone is conducted. The mechanism of post-polio fatigue, a common and disabling symptom in many patients, is under study. The spectrum of neuromuscular disorders associated with HIV infection has been studied and the role of the virus as the cause of neuropathy or myopathy is investigated with a variety of immunocytochemical studies, in situ hybridization and PCR. The antiretroviral drug AZT was found to cause a specific myopathy with abnormal mitochondria on the basis of various morphologic, molecular, biochemical and immunocytochemical studies. A longitudinal study of HIV- positive patients that develop myopathic symptoms while on AZT is conducted with serial muscle biopsies to assess factors associated with the development of myopathy and design effective therapies. The metabolic basis of fatigue is studied in patients with mitochondrial myopathies, post-polio syndrome, chronic fatigue syndrome and HIV- or AZT-associated myopathies using exercise magnetic resonance spectroscopy. Randomized-controlled clinical trials are conducted with high-dose intravenous immunoglobulin (IVIg) in patients with PM/DM, chronic inflammatory and paraproteinemic demyelinating polyneuropathies and ALS. A controlled study using dichlorophenamide, a carbonic anhydrase inhibitor, is ready to begin in patients with hypokalemic periodic paralysis.