Ginger (Zingiber officinale) is a universally known food plant reputed for its medicinal use in gastrointestinal disorders as a prokinetic and laxative. We recently showed that 70% aqueous-methanolic extract of ginger (Zo.Cr) exhibits prokinetic activity in rats via activation of post-synaptic muscarinic M3 receptor in rat stomach fundus. In view of the physiological significance of pre-synaptic muscarinic M1 and M2 autoreceptors, this study was undertaken to further look into the possible mode of action of the prokinetic effect of ginger through inhibition of pre-synaptic muscarinic receptors. Isolated tissue bath experiments were performed with Sprague-Dawley rat stomach fundus strip preparations immersed in Kreb's solution at 37 degrees C. Carbachol (CCh) maximum responses (1 microM) were obtained in rat stomach fundus. Zo.Cr, given in multiple increasing bolus concentrations (0.01-0.1 mg/ml) 10 min prior to administration of CCh, potentiated the CCh peak responses showing that it is possibly inhibiting the pre-synaptic muscarinic receptors. Like wise, increasing bolus concentrations of pirenzepine (0.03-0.3 microM) and himbacine (0.01-0.03 microM), standard muscarinic M1 and M2 antagonists respectively, also potentiated the CCh responses. These results show that ginger, in addition to having a direct cholinergic agonistic effect on the post-synaptic M3 receptors, also has a possible inhibitory effect on pre-synaptic muscarinic autoreceptors, similar to standard muscarinic antagonists, thus reiterating the gastric stimulant effect of this age-old plant.