The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. Cimetidine is an H2 receptor antagonist and a potent inhibitor of Na+/H+ antiporter, which is found in the plasma membranes of various cell types, including mesothelial cells. Recent reports linked Na+/H+ antiporter stimulation with increasing peritoneal fibroblast proliferation. The aim of the present study was to investigate by means of Ussing chamber experiments the effect of cimetidine on the transmesothelial electrical resistance (R) of isolated visceral sheep peritoneum. Peritoneal samples obtained from adult sheep were collected from the slaughterhouse and transferred in oxygenated Krebs-Ringer bicarbonate (KRB) solution to the laboratory within 30 minutes of the animal's death. The peritoneal tissue was transferred in a cooled KRB solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A planar sheet of the visceral peritoneum was mounted in an Ussing-type chamber and cimetidine (10(-3) mol/L) was added to the solution on the apical and basolateral sides. The R was measured before and for 15 minutes serially after addition of the cimetidine. Results presented are the means +/- standard error of the mean of 12 experiments. Addition of cimetidine basolaterally induced, within 1 minute, an increase in the deltaR of 35.97% +/- 12.01% (p < 0.05), which returned to baseline after 15 minutes. The action of cimetidine on the apical side of the membrane was similar, with a rapid rise in the deltaR of 47.3% +/- 16.4% (p < 0.05) and a subsequent decline to control values. The R is inversely correlated with membrane permeability. The results of the present study indicate a rapid action of cimetidine on the permeability of visceral sheep peritoneum, probably through inhibition of mesothelial Na+/H+ antiporter. The increase in R observed after addition of the cimetidine clearly indicates the existence of Na+/H+ antiporter on both sides of visceral sheep peritoneum. The clinical implications of our results should be further investigated.