The influence of electrolyte concentrations on the action of morphine and naloxone was studied in the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum to examine whether opiate receptor binding obseved in vitro with homogenates represents binding to the pharmacological receptor. The preparations were suspended in a modified Krebs-Henseleit bicarbonate buffer solution and electrically stimulated at 0.2 Hz. Morphine inhibited electrically evoked contractions; the concentration of morphine required for a 50-percent inhibition was 190 nM. This inhibitory action of morphine was potentiated in a medium containing lower concentrations of : Na⁺ or K⁺, or by the addition of Mn²⁺ to the medium, and weakened by increasing the concentration of Ca²⁺ or decreasing the concentration of Mg²⁺. Naloxone antagonized these actions of morphine: however, pA₂values for naloxone (indices of affinity for antagonists, approximately 8.8) were unaffected by these electrolyte concentrations. Thus, changes in the inhibitory action of morphine caused by alterations in electrolyte concentrations are probably not the result of changes in the affinity of the receptor for opiates, but due to alterations in the events which precede or follow the receptor binding. Effects of electrolytes on the affinity of the functional opiate receptor for naloxone in guinea-pig ileum are apparently different from those reported with the specific binding sites for opiates in brain homogenate.