The mesothelium is part of the peritoneal water and ion transport barrier essential for peritoneal dialysis (PD) treatment and has a central role in the pathogenesis of peritoneal fibrosis and ultrafiltration failure observed in many PD patients. We investigated the effect of amiloride on the transmesothelial electrical resistance (RTM) of isolated parietal human peritoneum. Intact sheets were obtained from seven patients (three men, four women; mean age, 64 +/- 8 years). Fourteen peritoneal planar sheets were transferred to the laboratory in oxygenated Krebs-Ringer bicarbonate solution at 4 degrees C within 30 minutes after removal and mounted in an Ussing-type chamber. Amiloride (10(-3) mol/L) added apically (n = 8) caused a rapid rise of the RTM to 24.15 +/- 0.76 [OMEGA]H cm2 and a subsequent value persistence (p < 0.05); added basolaterally (n = 6), it increased the RTM to 22.66 +/- 0.59 [OMEGA]H cm2 within 1 minute, which persisted throughout the experiment. RTM was measured before and serially for 30 minutes after addition of amiloride. Control RTM was 20.29 +/- 0.86 [OMEGA]H cm2. These results indicate a rapid inhibitory effect of amiloride on the ionic permeability of parietal human peritoneum. The increase in the RTM observed after addition of amiloride clearly indicates the existence of amiloride-sensitive sodium channels on the human parietal peritoneal membrane, which may play some role in the ultrafiltration process and sodium removal during PD.