Interleukin (IL)-10 is a type-2 T-helper cell cytokine with a broad spectrum of anti-inflammatory actions. Inflammation plays an important role in the pathogenesis of chronic obstructive pulmonary disease. It was hypothesised that single nucleotide polymorphisms (SNPs) of the genes encoding IL-10 (IL10) and the alpha subunit of its receptor (IL10RA) are associated with changes in, or value of, forced expiratory volume in one second (FEV1) in smoking-induced chronic obstructive pulmonary disease. In total, eleven SNPs of IL10 and IL10RA were studied in 586 White subjects, selected from continuous smokers followed for 5 yrs in the Lung Health Study, who showed the fastest (n=280) and slowest (n=306) decline in FEV1. These 11 SNPs were also studied in 1,072 participants exhibiting the lowest (n=538) and highest (n=534) baseline FEV1 at the beginning of the Lung Health Study. No association was found in the primary analyses. Although a subgroup analysis showed that the IL-10 3368A allele was associated with a fast decline in FEV1, the association did not pass correction for multiple comparisons. No gene-gene interaction of IL10 with IL10RA was found. There was no association of polymorphisms of the genes encoding interleukin-10 and the alpha subunit of its receptor with the rate of decline in, or value of, forced expiratory volume in one second in smoking-induced chronic obstructive pulmonary disease.