Astemizole, one of the newer generation of nonsedating antihistamines, was evaluated in a double-blind study of forty-six patients who had chronic idiopathic urticaria with or without angioedema; most had severe disease. Nineteen of twenty-three patients who were on placebo discontinued treatment because of lack of response compared to only five of twenty-three astemizole-treated patients (p less than 0.0001). Fourteen of twenty-two astemizole-treated patients and two of twenty-two placebo-treated patients considered the results to be good or excellent (p less than 0.0001). Blinded assessment by the investigators yielded similar results (p less than 0.0001). Therapeutic response was the same in patients with and without angioedema in addition to urticaria and in those requiring corticosteroids. Duration of urticaria also did not influence the results. Increased appetite and weight gain were the main side effects reported more frequently in the astemizole-treated than in the placebo-treated group, and no significant toxicity was noted. Follow-up after terminating the drug study indicated a high frequency of remissions during the subsequent year.