Since melatonin receptors are present in the intestines, the possibility that this hormone may affect intestinal motility has been studied in the rat. Sprague-Dawley male rats were given a carmine cochineal powder meal and were injected intraperitoneally with 1, 10, 100, or 1000 microg/kg melatonin. Sixty minutes after treatment, intestinal transit was found to be faster in animals treated with small doses of melatonin (1 or 10 microg/kg) than in saline-injected controls. This effect, however, appear to be clearly reversed with 100 or 1000 microg/kg melatonin. In fact, these doses of the hormone reduced intestinal transit in rats. The nonselective melatonin receptor antagonist, luzindole (administered intraperitoneally in a dose of 0.25 mg/kg, 15 min prior to melatonin injection) totally prevented the accelerating effect of melatonin (10 microg/kg) on intestinal transit. Luzindole per se failed to affect gut motility. Injection of the reversible acetylcholinesterase inhibitor and cholinergic agent, neostigmine, accelerated intestinal transit but failed to influence melatonin effect on this parameter. In contrast, intraperitoneal injection of the muscarinic receptor antagonist atropine delayed intestinal transit per se but did not reduce the stimulating effect of melatonin on this parameter. Intestinal myoelectrical recording revealed that intestinal myoelectrical activity was increased by intraperitoneal injection of melatonin (10 microg/kg). Administration of luzindole totally prevented melatonin-induced increase of intestinal myoelectrical activity. These results indicate that melatonin may affect intestinal motility in rats when administered in small doses. This effect might be mediated by melatonin receptors in the intestines, although the involvement of central receptors for the hormone is also possible.