By use of microelectrode techniques the electrical resistances of the cell membranes and paracellular pathways of surface epithelium in Necturus antrum were determined under control conditions (Ringer solutions containing 106.6 mM Na+, 91.4 mM Cl-) and during exposure to mucosal solutions containing high Na+ and Cl- concentrations. Resistances were determined by briefly exposing tissues to mucosal solutions containing 10(-4) M amiloride, a reversible inhibitor of Na+ conductances. Under control conditions in eight tissues, measurements obtained by exposure to amiloride were not significantly different from those obtained by an independent method, intraepithelial cable analysis, thus indicating the validity of the measurements obtained by the amiloride method. In 10 tissues, high luminal NaCl concentrations (Ringer salts + 125 mM NaCl) increased the apical cell membrane resistance from 5,778 +/- 267 to 7,714 +/- 422 omega X cm2 (P less than 0.01) and the basolateral membrane resistance from 2,973 +/- 186 to 3,869 +/- 335 omega X cm2 (P less than 0.01). The resistance of the paracellular pathway decreased from 625 +/- 13 to 505 +/- 13 omega X cm2 (P less than 0.001). Similar alterations in these resistances were observed when Na+ or Cl- were increased individually, when added as salts of isethionate- and N-methyl-D-glucamine+, respectively. These effects were not attributable to increases in luminal osmolarity, since mucosal solutions made equally hyperosmotic with 250 mM sucrose elicited increases in paracellular pathway resistance and decreases in resistances of the cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)