The purpose of this study was to determine if LPS had any effect upon the bioelectric responses of guinea-pig tracheal epithelium to serosally - and mucosally - applied indomethacin and hypertonic NaCl. Guinea-pigs were injected with LPS (4 mg/kg, i.p.) or saline, and 18 hours later epithelial bioelectric responses were measured in vitro using the guinea-pig isolated perfused trachea apparatus, which allows addition of pharmacological agents separately to either the serosal or mucosal surfaces. Previously, our laboratory has shown that the basal transepithelial potential difference (V ms) in LPS-treated animals is significantly hyperpolarized compared to control. In both saline-and LPS-treated animals, the simultaneous addition of indomethacin to the serosal and mucosal baths depolarized the V ms, but significantly more so in the LPS-treated group: +1.88 mV (+/- 0.31) and +5.57 mV (+/- 1.37) for saline- and LPS-treated animals, respectively. In both saline and LPS-treated groups, serosally- and mucosally-applied NaCl depolarized the V ms. Within both treatment groups, NaCl was more potent serosally than mucosally. In addition, NaCl depolarized the V ms more in the LPS-treated group that in the control group. These results indicate the cyclooxygenase products may contribue to the hyperpolarization of the V ms in the airway epithelium after LPS-treatment. In addition, the epithelium acts as an osmotic sensor by depolarizing in response to serosally- and mucosally- applied hypertonic NaCl, with the serosal side being a more sensitive osmotic sensor.