Background: Special regulatory role of prostaglandin E2 (PGE2) has been postulated in aspirin-induced asthma. Objective: To investigate effects of aspirin (nonselective COX inhibitor) and celecoxib (selective COX-2 inhibitor) on systemic production of prostaglandin E2 and cysteinlyl leukotrienes (cys-LTs) in patients with asthma. Methods: We determined urinary concentrations of: 1) two main PGE2 metabolites, i.e.:13,14-dihydro-15keto-PGE2 using commercial enzyme immunoassay (EIA) and 9,15-dioxo-11α-hydroxy-2,3,4,5- tetranor-prostane-1,20-dioic acid using gas chromatography/mass spectrometry and 2) leukotriene E4 (LTE4) using EIA. Determinations were performed at baseline and following oral aspirin, and celecoxib challenges, carried one week apart, in two well-defined phenotypes of asthma: aspirin-induced asthma (AIA) and aspirin-tolerant asthmatics (ATA). Results: At baseline mean prostaglandin E2 metabolites values did not differ between the groups. Following aspirin challenge they both became significantly depressed in ATA group, but their mean level remained unchanged in AIA group. The dose of aspirin had no effect on magnitude of the response of the PGE2 metabolites and its duration. In both study groups urinary prostaglandin E2 metabolites decreased following celecoxib challenge. No correlation was found between the levels of PGE2 metabolites and LTE4. Conclusion: Aspirin- ; precipitated asthmatic attacks are not associated with changes in the systemic prostaglandin E2 production. In contrast, prostaglandin E2 systemic production becomes depressed by aspirin in the ATA.