Thirty dogs with atopic dermatitis were given tepoxalin (Zubrin®, Intervet/Schering-Plough Animal Health, Boxmeer, the Netherlands) or placebo once daily for 4 weeks, followed by a wash-out period of 1 week before reversing the treatments. Pruritus was scored by the owners using the Edinburgh Pruritus Scale and one investigator employed a modification of the Canine Atopic Dermatitis Extent and Severity Index-01 (mCADESI-01) to score the physical lesions. After administration of tepoxalin there was a ≥ 50% reduction in pruritus and mCADESI-01 scores in 36% and 25% of the dogs, respectively, whereas following administration of the placebo there was a ≥ 50% reduction in pruritus and mCADESI-01 scores in only 25% and 16% of the dogs, respectively. Analysis of pooled data indicated that tepoxalin resulted in a significant reduction in pruritus (P = 0.012) and mCADESI-01 (P = 0.002) scores but there was no significant change after placebo. The median pruritus scores before and after tepoxalin were 2 (range 1–5) and 1 (range 0–5), respectively, and before and after placebo were 2 (range 0–4) and 2 (range 0–4), respectively. The median mCADESI scores before and after tepoxalin were 23 (range 0–68) and 16 (range 0–72), respectively, and before and after placebo were 18 (range 3–79) and 24 (range 0–65), respectively. At the dose used in this study (10.0–19.1 mg kg−1), tepoxalin was well-tolerated and no adverse effects were noted.