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Morphine has been shown to release 5-hydroxytryptamine (5-HT) from the intestinal wall of dogs. The 5-HT released is suspected to be the mediator of the contractile effect of the narcotic-analgesics in the intestine, probably by acting upon post-ganglionic cells of the myenteric plexus. In this paper it is shown that the depolarizing agents nicotine and DMPP block the contractile response of the dog intestine in vivo, to intra-arterially injected 5-HT, dextromoramide and morphine. Previous treatment by hexamethonium prevented the blocking effect of DMPP and nicotine. These results suggested that the depolarization of the ganglionic cells, rather than the blockade of the cholinergic receptors, is responsible for the blockade of 5-HT and morphine effects by DMPP and nicotine.