Since erythromycin was shown to be effective in the treatment of patients with diffuse panbronchiolitits, newly discovered effects of macrolide antibiotics have attracted much attention. It was reported that erythromycin inhibits Cl secretion across cultured canine tracheal epithelial cells. Erythromycin may decrease the movement of water toward the lumen, thus reducing sputum volume. We tested the hypothesis that erythromycin and clarithromycin have a similar effect on the dissected canine tracheal epithelium, by measuring the short circuit current using Ussing chambers. Addition of erythromycin or clarithromycin did not change the short circuit current within 20 minutes when applied on either the mucosal side or the submucosal side. No changes in the short circuit current were observed after pretreatment of the epithelium with amiloride, an Na channel blocker, or bumetanide, a Cl transport inhibitor, and subsequent addition of the macrolide antibiotics. These data indicate that neither erythromycin nor clarithromycin has any short term effect on ion transport in the dissected canine tracheal epithelium.