During annual medical monitoring, some firefighters are found to have rates of decline in forced expiratory volume in one second (FEV1) far exceeding their peers. Interleukin-10 (IL-10) suppresses inflammation, and single nucleotide polymorphisms (SNPs) in the IL-10 gene may confer variable susceptibility to more rapid decline in lung function. In 1204 firefighters with at least six annual FEV1 measurements, increased age and greater initial FEV1 were associated with more rapid decline in lung function. DNA collected from 379 of these firefighters was screened for IL-10 SNPs at -1117, -854, 919, 1668, and 1812. A statistically significant difference in decline in lung function was found based on genotyping at the 1668 SNP. Evaluation of gene polymorphisms regulating lung inflammation may help to explain some of the variation in rate of decline in lung function in firefighters.