Fexofenadine, a histamine H1-receptor antagonist, is approved for the treatment of pruritus associated with atopic dermatitis. The effects of fexofenadine on scratching behaviour, and plasma levels of histamine and eotaxin were assessed in a new model of atopic dermatitis. Mice fed a diet low in Mg2+ and Zn2+ (special diet S) were compared with mice on a normal diet (N) or diet S plus fexofenadine HCl for weeks 0-10 (S + F(0-10)), 0-5 (S + F(0-5)) or 6 - 10 (S + F(6-10)) (seven mice per group). Compared with group N, group S mice showed significantly greater scratching frequency, and plasma histamine and eotaxin concentrations; these three variables were significantly lower in group S + F(0-10) than in group S. Scratching frequency increased when fexofenadine was discontinued. Fexofenadine significantly reduced mast cell and eosinophil numbers. Histamine may be important in the pathological changes seen in this model of atopic dermatitis, suggesting that it might aid future development of antihistamines for the treatment of atopic dermatitis.