Abstract—Products of the 5‐lipoxygenase metabolic pathway may be important mediators of inflammation in canine skin. Pharmacologic blockade of this pathway may therefore decrease clinical signs associated with canine atopy. To test this hypothesis, 31 dogs were entered on a randomized, double‐blind, placebo‐controlled, crossover trial to assess the efficacy of an investigational oral 5‐lipoxygenase inhibitor (WY‐50295) in treating canine atopy. Dogs were treated for 11 days with the drug and 11 days with the placebo, in random order, with a 3‐day washout period between the treatment periods. Clinical signs were assessed daily by the owner in all 31 dogs, using a subjective scoring scale. Twelve of the dogs were additionally evaluated at intervals by the investigators and similarly scored. Analysis of variance revealed no significant differences (P>0.05) in owner or investigator scores assigned during placebo treatment, drug treatment, and no treatment periods. In an end‐of‐study evaluation, 24.1 per cent of owners reported satisfactory response to placebo capsules and 17.2 per cent reported satisfactory response to the drug, demonstrating a strong placebo effect. Short‐duration treatment with WY‐50295 did not appear to be effective in reducing cl