Cyclooxygenase-1 (COX-1) regulates the biosynthesis of prostaglandins, which are important mediators in asthma. The possible association of COX-1 gene polymorphisms with asthma has not been investigated.The allele frequencies of 20 COX-1 polymorphisms were determined in a random Australian Caucasian population using MassARRAY technology. Informative and potentially functional promoter (c.8592C>T, c.1676C>T) and coding region (c.22C>T, c.50C>T) polymorphisms were investigated in carefully phenotyped patients with mild (n=316), moderate (n=241), severe (n=86) or aspirin-intolerant asthma (AIA) (n=58), and in nonasthmatic subjects (n=477).There were no allelic, genotypic or haplotypic associations between these four polymorphisms and asthma or asthma severity. Over-representation of the c.50TT genotype among AIA patients (3.4%) compared with aspirin-tolerant patients (0.8%), and a global haplotype association with AIA did not reach statistical significance. The c.22TT genotype was less frequent among atopic (0.1%) rather than nonatopic individuals (1.2%; odds ratio=9.05, 95% confidence interval 1.01-81.29).In conclusion, the present investigation of cyclooxygenase-1 polymorphisms in asthma indicates that they do not appear to play a substantial role in genetic pre-disposition for asthma or asthma severity. However, the c.22TT genotype confers a small protective effect against atopy. Potential associations with aspirin-intolerant asthma were identified and warrant further investigation in a larger population of aspirin-intolerant asthma patients.