In an in-vitro preparation of gastric mucosae of Rana pipiens, the effect of adding melittin to a concentration of 5×10 −6 M in the secretory solution on the transepithelial potential difference ( PD), resistance ( R) and short-circuit current ( I sc) was studied. In 20 min, melittin decreased the PD by 9.3 mV and R by 148 ohm cm 2. These changes can be explained by a decrease in the resistance, R P, of the paracellular pathway. To determine whether specific-ion pathways were responsible for the decrease in R, the effect of melittin on the partial conductances of Cl −, K + and Na + was also studied using the ion substitution method. Melittin decreased the PD response to changes in nutrient Na +, K + and Cl − and the PD response to changes in secretory Cl −, but did not affect PD responses to changes in secretory Na + or K +. Therefore, melittin decreased the nutrient membrane partial conductances of Cl −, K + and Na + and secretory membrane partial conductance of Cl −, without affecting the secretory partial conductances of Na + or K +. Initially, melittin increased I sc in regular and Cl −-free but not in Na +-free solutions. There was a delayed decrease in I sc. The results indicate that melittin decreases R P, increases the Na + conductance of the secretory membrane and inhibits, eventually, the Na +/K +-ATPase pump.