The difference in the complete fatigue or exhaustion of a muscle-nerve prepn. by electrical stimulation and the apparent fatigue curve from voluntary contractions of the muscle in a human is emphasized. A protective feed-back mechanism in the living organism prevents the former state from ever occurring. There are 4 sites in the neuro-muscular system of man where the symptoms of fatigue are produced: in the muscle itself from atrophy or disease; in the myoneural-junction (myasthenia gravis); in the lower motor neuron (neuritis); in the central nervous system from interference of motivation from either structural disease in the brain or from blocking of volitional effort by emotional causes. Neostigmine is effective in only the myoneural-junction type. In others, it decreases the performance.