Background: Little is known about the course of aspirininduced urticaria. A special regulatory role of cysteinyl leukotrienes and prostaglandin D2 (PGD2) has been postulated. Objective: We performed a long-term observation on clinical course, aspirin sensitivity, and urinary eicosanoids in patients with aspirin-induced urticaria. Methods: For 4 years, we followed up 22 patients with chronic idiopathic urticaria and aspirin hypersensitivity who restrained from the use of aspirin and other COX-1 inhibitors. Aspirin challenges were performed in 2002 (all results were positive) and repeated in 2006. Levels of urinary leukotriene E4 (LTE4) and the main PGD2 metabolite, 9a11bPGF2, were measured at the same time points. Results: During the follow-up period, the severity of urticaria has decreased. In 14 of 22 patients, the results of aspirin challenge remained positive. In 2002, these 14 patients responded to aspirin with a significant increase in urinary LTE4 and 9a11bPGF2 levels. When studied 4 years later, they showed a similar response of 9a11bPGF2 (P 5 .047) and a tendency toward an increase in LTE4 level (P 5 .057). There was a correlation between the urinary LTE4 concentration after aspirin challenge and the intensity of skin eruptions. The dose of aspirin had no effect on the magnitude of response of both LTE4 and the PGD2 metabolite. In the remaining 8 patients, negative aspirin challenge results were not associated with changes in the urinary eicosanoids studied. Conclusions: Aspirin hypersensitivity manifesting as urticaria/ angioedema remains present after 4 years in about two thirds of patients. Aspirin-precipitated skin reactions associate with increased excretion of LTE4 and PGD2.