The illness known as chronic fatigue syndrome (CFS), has over the years been referred to by a variety of names. The defining characteristic of M.E. is that patients suffer after physical exertion and develop disease progression with continued physical exertion. The defining characteristic is exercise intolerance, post-exertional muscle weakness, generalized weakness, faintness, and pain; and post-exertional relapsing of symptoms. In some cases symptoms remit with rest, and in other cases they do not.

Recent research on a prominent subset of the illness showed that postural stress and exercise exacerbated cardiac insufficiency in this disease. If a patient improves with exercise, that patient does not have M.E. and may have some illness other than M.E. (for example, arthritis, depression, osteoporosis, and a number of medical conditions do improve with exercise).

In addition to the above central characteristic, M.E. is characterized by three main components:

(1) Muscle weakness and a delayed or impaired recovery of muscle function after exercise. This could also include a subset of cardiomyopathy under our research-updated interpretive hypothesis.
(2) Circulatory impairment. This could include coagulopathy, abnormal erythrocyte morphology, or both, and other factors affecting the circulatory system such as dysautonomia and low plasma and/or erythrocyte volume, the latter resulting in orthostatic intolerance.
(3) Cerebral involvement: encephalopathy, encephalitis, neurological, and neuropsychiatric impairment.

While all three must be present for a diagnosis of M.E., some patients' symptoms may be brain predominant, others muscle predominant, etc.

Other symptoms include post-exertional malaise and fatigue, sleep dysfunction, and pain; neurological, neurocognitive, dysautonomic, neuroendocrine, cardiac, and immune manifestations.

The symptoms of the disease are exacerbated by physical exertion, mental exertion, mental stress, or orthostatic stress. In severe cases, even slight orthostatic stress triggers relapses. Symptoms may range from mild, to severe, to life-threatening (such as tachyarrythmias or siezures). The level of activity that precipitates these symptoms may vary greatly in afflicted individuals, and the symptoms that relapse may vary. They may include: sore throat, flu, fever, chills, body aches, sweats, low body temperature, lymphadenopathy, muscle weakness, muscle pain, hypoglycemia, weight change, nausea, vomiting, vertigo, chest aches, chest pain, cardiac arrhythmia, resting tachycardia, orthostatic tachycardia, orthostatic fainting or faintness, opthalmoplegia, eye pain, stroke-like episodes, difficulty swallowing, paresthesias, peripheral neuropathy pain, polyneuropathy, extreme pallor, sleep disorder, myoclonus, hyperreflexia, temporal lobe and other types of seizures, cognitive, memory and concentration impairment, attention deficit, anxiety, confusion, disorientation, light/sound sensitivity, blurred vision, wavy visual field, and other visual and neurological disturbances. Allergic hypersensitivity is also common in the disease.