Abstract Cetirizine, a peripheral H 1 antagonist, was administered to patients with delayed pressure urticaria in a double-blind, placebo-controlled, crossover study. Efficacy in reducing pressure-induced wheals and flares was evaluated. Histologic changes were also assessed with the skin window technique in weight-induced wheals. Results showed a statistically significant reduction in weight-induced wheal area ( p < 0.01) after cetirizine therapy; this improvement was accompanied by a concomitant reduction in eosinophil recruitment as demonstrated by the skin window technique ( p = 0.0029). Subsequently, 14 patients with delayed pressure urticaria underwent biopsy before and after 3 weeks of cetirizine therapy to evaluate the drug's histologic effects. A blinded observer performed the histologic studies. Weight-induced lesions showed a mixed inflammatory infiltrate, primarily polymorphonuclear (neutrophils and eosinophils), whereas the unchallenged skin sites were normal. Cell counts from pressure-induced lesions showed a significant reduction in eosinophils after cetirizine treatment.