In an in-vitro preparation of gastric mucosae of Rana pipiens, the effect of adding melittin to a concentration of 5 x 10(-6) M in the secretory solution on the transepithelial potential difference (PD), resistance (R) and short-circuit current (I-SC) was studied, In 20min, 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. (C) 1998 Elsevier Science B.V.