Background: In patients with pruritus of cholestasis, response to conventional drug treatment may be unsatisfactory. Activation of 5-hydroxytryptamine receptors on dermal sensory nerve-endings plays a role in the perception of pruritus. The 5-hydroxytryptamine 3 receptor antagonist, ondansetron, has been used in the treatment of pruritus of cholestasis, but there are few controlled data. Aim: To determine whether ondansetron is effective in treating the pruritus of cholestasis. Methods: A total of 19 patients with resistant pruritus were randomized, double blind, to receive either on-