Abstract The actions of two mercury compounds, HgCl 2 and methyl mercury chloride (MeHg), and of CdCl 2 on the epithelium of the rat colon were studied with the whole-cell patch-clamp technique and the Ussing chamber. MeHg (50 μ m) induced an increase of membrane outward current ( I out) in enterocytes of isolated crypts patched from the basolateral side. This action was inhibited by a Cl − channel blocker and a K + channel blocker, indicating an increase of both the Cl − and the K + conductance. In contrast, HgCl 2 (50 μ m) did not affect I out, whereas CdCl 2 (50 μ m) decreased it slightly. In mucosal preparations all three compounds induced a concentration-dependent increase in shortcircuit current ( I sc) when administered to the serosal, i.e., contraluminal side. Sensitivity to chloride transport blockers and anion replacement experiments revealed that the increase in I sc represented Cl − secretion. In contrast to the actions of luminally applied mercury compounds, the increase of tissue conductance ( G t) was only small. Tetrodotoxin and indomethacin suppressed the effect of the metal compounds on I sc and G t, while atropine diminished it only partly. This indicates that the secretory action of these heavy metals has not only a direct effect on epithelial cells but is also mediated by prostaglandins and cholinergic and noncholinergic neurons.