The idiopathic inflammatory myopathies (IIMs) encompass a group of muscle disorders of unknown origin and pathogenesis characterized by symmetrical, proximal muscle weakness and by inflammatory infiltrates in muscle tissue. The mechanisms behind the loss of muscle function are largely unknown. It is often anticipated that the muscle weakness is caused by the inflammatory cells. However, inflammatory infiltrates are not always present in the muscle tissue and the infiltrates sometimes have a patchy distribution, which makes it difficult to explain the generalized muscle weakness merely by infiltration of inflammatory cells. We investigated patients at different stages of myositis: early myositis without detectable inflammatory infiltrates, active myositis with pronounced inflammatory infiltrates and chronic myositis with persisting muscle weakness but without detectable inflammatory cells in muscle tissues. In these studies, a better correlation was observed between the clinical symptoms and involvement of the capillaries with expression of the cytokine interleukin (IL)-1alpha and by the presence of major histocompatibility complex (MHC) class I expression on muscle fibres. Whether these molecules could affect muscle function is not known. Using phosphorus P-31 magnetic resonance spectroscopy decreased values of adenosine triphosphate (ATP) and phosphocreatine (PCr) levels were observed at rest. These metabolic abnormalities were further accentuated by exercise and increased PCr levels correlated with improved clinical status. The underlying mechanisms responsible for these biochemical abnormalities have not been defined but could be related to a disturbed tissue oxygenation.