The effects induced by metoclopramide (MCP) were examined in transverse muscular strips from pigeon oesophagus. MCP (0.1 nM-10 microM) induced a concentration-dependent excitatory effect on the EMG activity, characterized mainly by an increase in the spike burst frequency. Such an excitatory effect was fully antagonized by tetrodotoxin and partially antagonized by atropine, by naloxone and by desensitization of the preparation to 5-hydroxytryptamine (5-HT). The atropine-resistant excitatory component was not modified by guanethidine. The combination of naloxone and atropine was more effective than a single antagonist in blocking the response to MCP. The combination of naloxone and 5-HT desensitization failed to further reduce the MCP-induced excitatory effect. The present results indicate that the excitatory effects of MCP are mediated via neural elements. MCP activates both cholinergic and non-cholinergic, non-adrenergic excitatory neurons. Furthermore, results suggest that serotoninergic and opioid neural pathways might be involved in the excitatory effects of MCP.