A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as the most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesised that the type IV collagen a3 (COL4A3) gene, which is one of the genes located in the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD.To test this hypothesis, the association of COL4A3 -1162T.C, IVS2+12C.A, P141L, G162E, H451R, P574L and *315C.A polymorphisms with the risk of COPD was investigated in a casecontrol study of 311 COPD patients and 386 controls.The presence of at least one 451R allele was associated with a significantly higher risk of COPD compared with the 451 H/H genotype (adjusted odds ratio 1.48, 95% confidence interval (1.03-2.14)). When the subjects were stratified according to age and COPD severity, the 451R allele was associated with a significantly higher risk of COPD only in younger individuals with severe COPD (3.02 (1.37-6.67)).In conclusion, these findings suggest that the type IV collagen a3 gene contributes to the genetic susceptibility to chronic obstructive pulmonary disease.