Cold urticaria is a rare condition characterized by abnormal wealing following exposure to cold. It has been suggested that lipid-derived mediators may be involved in the pathogenesis of this condition. We have investigated whether the inflammatory reaction in cold urticaria is associated with the release of cysteinyl-leukotrienes. Leukotriene E4 (LTE4; a stable metabolic product of LTC4 and LTD4) and histamine were measured in the blood draining the site of a cold-challenge in five patients with clinical histories of cold urticaria. Three of the patients showed a typical clinical response to the challenge, and this was associated with an increase in the concentration of LTE4 and histamine. No increase in LTE4 or histamine levels were observed following cold challenge in the non-responding individuals.