BACKGROUND: Postoperative nausea and vomiting (PONV) is the most frequent and discomforting side effect following general anesthesia. Most volatile anesthetics have a potent effect on serotonin (5-hydroxydtryptamine, 5-HT) type 3 receptor mediating PONV, and their antagonists have been currently used effectively to prevent and/or reduce the incidence and severity of PONV. The authors reported previously that ginsenosides have inhibitory effect on 5-HT3A receptor. In this study we intended to elucidate the inhibitory effect of ginsenosides on the potentiated 5-HT3A receptor by desflurane. METHODS: After in vitro transcription of the recombinant mouse 5-HT3A receptor in the Xenopus laevis oocyte, we examined the effects of ginsenosides (g-Rb1, g-Rg1, g-Rd, g-Rg2) as well as ginsenoside metabolite, compound K on the modulation of desflurane by measuring currents flowing through 5-HT3A receptor using two-electrode voltage clamp technique. RESULTS: Although normalized inhibitory responses of ginsenosides were same regardless of desflurane, some ginsenosides such as g-Rd, g-Rg2, and g-Rg1 showed potential inhibition to the enhanced 5-HT induced current of 5-HT3A receptor by desflurane. CONCLUSIONS: Although ginsenosides have substantial inhibitory effect on 5-HT3A receptor, the effects of ginsenoside on potentiation by desflurane of 5-HT induced current via recombinant 5HT3A receptor may depend on the types of ginsenoside, which suggesting that ginsenoside might have an antagonistic action to nausea and vomiting associated with volatile anesthetics.