The aim of the present study was to investigate whether low glucose and pH level, which are usually measured in complicated pleural effusions, alter the electrochemical function of healthy human parietal pleura. Parietal pleural pieces were stripped from 66 patients during thoracic surgery and were mounted in Ussing chambers. Krebs' solutions containing different glucose levels (0, 40 and 100 mg) and balanced at different pH levels (7.4, 7.3 and 7.2) were added to the pleural cavity surface of the pieces. Transmesothelial potential difference was measured at various time-points as an electrophysiological variable and transmesothelial resistance (R(TM)) was calculated using Ohm's law. When normal-glucose Krebs at pH 7.45 was used, R(TM) remained unchanged over time, but when low-glucose Krebs was used, R(TM) decreased. Krebs without glucose caused the greatest decrease in R(TM). Use of low-pH Krebs decreased R(TM). The lower the pH of the Krebs, the faster the decrease in R(TM) and the greater the effect. The decrease in R(TM) was greater with low-pH than with low-glucose Krebs. Low glucose and low pH caused an additive decrease in R(TM). Low glucose concentration and low pH cause alteration of the electrochemical function of human parietal pleura and could act as agents that lead to further exudate progression.