Two studies of the additional effect of an H2 receptor antagonist when given in combination with an H1 antagonist were undertaken in dermographic urticaria. Using a randomized, double-blind, crossover design in 19 patients, a combination of cetirizine (10 mg at night) and ranitidine (150 mg twice daily) was compared with a combination of cetirizine (10 mg at night) and placebo. The addition of ranitidine did not produce any significant difference in linear analogue scores for weal, Itch or sleep disturbance. There was a significant depression of the frictional force/wealing response curve with an increase in wealing threshold (P<0.0001) following the addition of H2 blockade. The wealing threshold was 54.7 ± 4.4 (mean ± SEM) g/mm2 for the H1 antagonist alone, and 73.2 ± 5.7 for the combination of H1 and H2 antagonists. In a second similar study involving nine different patients, comparing terfenadine (120 mg twice daily) with a combination of terfenadine and ranitidine (150 mg twice daily), the weal threshold was 59.8 ± 6.6 for the H1 antagonist alone, and 73.0 ± 6.4 for the combination of H1 and H2 antagonists. Thus, in dermographic urticaria, adding an H2 antagonist to treatment with a potent H1 antagonist gives a small, significant reduction in wealing response, but no symptomatic benefit. We conclude that involvement of the H2 receptor in this urticarial disease is minimal, and does not justify the use of H2 receptor antagonists.