The clinical manifestations of acute poisoning by organophosphorus compounds in man are in accord with, initially, the stimulation and, later, the blocking of cholinergic transmission due to acetylcholinesterase inhibition. The manifestations involve mainly the para-sympathetic nerves, the neuromuscular junctions, and the central nerve synapses, and to a smaller degree the cholinergic sympathetic nerves. Miosis and muscle fasciculations are useful signs for diagnosis and for the control of therapy. Blood cholinesterase determination is the best diagnostic test. The cause of death is usually respiratory paralysis. Persistent manifestations have not been confirmed. Atropine and pralidoxime are effective for treatment and useful for diagnosis. Other oximes are promising but their clinical value has not been established. Poisoning by malathion is characterized by a prolonged course and by motor signs. Poisoning by organophosphorus compounds in man differs from animal experiments in several ways: in man, exposure may occur by several different routes, the manifestations are detected more easily, and therapy is given throughout the course of illness.