Two preparations of the hind‐leg of the locust have been used to investigate the physiological effect of chemicals on nerve muscle and on the central nervous system.In the first preparation, the isolated hind‐leg is made to kick regularly by electrical stimulation of the crural nerve. Test chemicals are perfused in saline solution through the femur.The second preparation makes use of a reflex synapsing in the metathoracic ganglion. A reflex retraction of the tibia of the hind‐leg is initiated by stimulating the tarsus by heat at regular intervals; the chemicals are applied in agar or paraffin blocks directly to the ganglion. In both cases the movements of the tibia or of the extensor or flexor tibialis muscles separately are recorded mechanically on a smoked drum.Acetylcholine has no action on the nervous system except for an unusual action on the nerve muscle preparation. Acetyl β‐methylcholine, carbamylcholine and benzoylcholine have no action on either preparation except at high concentration.Decamethonium andd‐tubocurarine had no effect on either preparation, while nicotine and eserine, after initial excitation, caused a simple reversible block in both preparations, the ganglion being affected at a lower concentration.Adrenalin and adrenergic drugs have no effect on either preparation.The organo‐phosphorus insecticides, parathion, paraoxon and TEPP, acted on the ganglion only and at low concentrations. Their main site of action is on the central nervous system.DDT affected ganglionic and nerve muscle preparations, whereas γ‐BHC acted rather similarly on the ganglion but had no effect on nerve muscle.There is no evidence for a cholinergic mechanism at the neuromuscular junction in the leg muscles. The ganglion, on the other hand, was markedly affected by the anticholinesterases tested, but acetylcholine and related cholinesterase substrates, and drugs which interfere with the action of acetylcholine in mammals, had no effect. Acetylcholine was still without effect when injected through the membrane sheathing the ganglion. On the other hand, micro injection experiments show that the sheath is relatively impermeable