A quantitative bioassay was used to determine that the nerve cord and head of the cockroach, Periplaneta americana (L.), contained the highest concentrations of Factor S; the legs and body contained lesser amounts. A twofold increase in the titre of Factor S was observed by spectrofluorometry and by bioassay in insects subjected to 4 hr of mechanical stress compared with the amounts in unstimulated insects. Houseflies, Musca domestica (L.), injected with 30 μg of the active substance were immediately paralysed: 60 per cent were unable to right themselves within 2 hr; the other 40 per cent showed a marked impairment in motor co-ordination. A substance that caused much the same biological response as Factor S was found in perfusates from electrically stimulated nerve cords of cockroaches. Exposure of the last abdominal ganglion of the cockroach to 8 μg of Factor S caused facilitation of the post-synaptic spike potential followed by after-discharges lasting 30 to 80 msec; 12 μg of the active residue partially blocked synaptic conduction. A parallel was drawn between the synaptic responses with increasing concentrations of Factor S and those occurring at progressive stages in stress paralysis. Factor S showed several properties typical of neurohormones, and an involvement in the mode of action of DDT is suggested. © 1969.