Muscle fiber degeneration and regeneration, inflammation in the intramuscular connective tissue and hypoxia in resting muscle are not necessarily associated with pain. However, when sustained or dynamic muscle contractions are performed in an ischaemic muscle, severe pain develops. In the chronic muscle pain syndrome called fibromyalgia (or fibrositis) the most likely cause of the pain is a combination of muscle tension and muscle hypoxia. This conclusion is supported by the finding of a pathological distribution of tissue oxygen pressure in painful muscles and a subjective feeling of muscle tension and muscle stiffness in the majority of patients. A decrease of high energy phosphates is found in biopsies from painful muscle. The most characteristic morphological finding is the so-called ragged red fiber, a finding that can be seen in mitochondrial disorders. The morphological and chemical findings are possibly a consequence of a long standing hypoxia. The possibility that sympathetic nerve activity is important for the development of chronic muscle pain is discussed.