The objective of this study was to investigate whether there is an association between IL1RN polymorphism and disease susceptibility for three age-related inflammatory conditions: polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and elderly-onset rheumatoid arthritis (EORA). A tandem-repeat polymorphism within IL1RN intron 2 was analyzed in 139 PMR, 69 GCA, and 156 RA patients (75 with EORA) as well as in 437 healthy subjects, together with the in vitro production of IL-1beta. Our results showed that the IL1RN*2/2 genotype was more frequent in PMR patients compared with controls (p = 0.032, odds ratio = 1.785, 95% confidence interval = 1.047-3.044) and GCA patients (p = 0.008, odds ratio = 4.661, 95% confidence interval = 1.352-16.065). We found no difference in the distribution of genotypes between PMR and EORA or between EORA and controls. However, the frequency of the IL-1RN*2/2 genotype had a tendency to be higher in patients with EORA compared with young onset RA. The presence of IL1RN*1 or IL1RN*2 allele was not associated with severity of the disease in PMR and GCA patients and did not influence the production of IL-1beta. In conclusion, the IL1RN*2 polymorphism in a homozygous state was associated with an increased susceptibility to PMR and may give some clues for a differential therapy with GCA.