Morphine depresses the twitch and tetanus of stimulated guinea-pig ileum by reducing acetylcholine released from cholinergic nerve endings. Acetylcholine output per shock falls to roughly the same residual amount at varying stimulation rates. Since normal output per shock declines with increasing stimulus frequency, the proportionate effect of morphine diminishes as stimulus frequency rises. Acute “tolerance” to morphine and a state of “morphine-dependence” can be produced. Phenadoxone, dihydromorphinone, metopon, methadone, and heroin are more active, codeine and pethidine less active, than morphine. Nalorphine also depresses the twitch and can desensitize the gut both to itself and to morphine.