The venom of the scorpion Leiurus quinquestriatus produced a significant, reversible inhibition of reconstituted Cl- channels of the small conductance type found in rat colonic epithelial cells. The kinetics of single-channel block by this venom were consistent with a first-order binding reaction in which the binding of one ligand molecule is sufficient to induce channel block. Single-channel mean block times were c.6 sec at -20 mV, and a KI in the submicromolar range is predicted. The active component has a mol. wt of roughly 5000 as judged by molecular sieve chromatography.