Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that has a dose-dependent anti-tumoral effect. Polymorphism in the MCP-1 distal regulatory region (-2518A/G) can affect the level of MCP-1 expression. We examined the polymorphisms of 112 unrelated patients with non-small-cell lung cancer (NSCLC) and 82 unrelated healthy controls of Han nationality in North China using PCR-RFLP. We found that the distributions of AA, AG and GG genotypes of MCP-1-2518 were significantly different in NSCLC patients compared to controls (chi(2) = 10.106, P = 0.006). There was a significant increase in the frequency of the AA genotype (odds ratio (OR) = 3.138, chi(2) = 8.905, P = 0.003) and a significant decrease in the frequency of the GG genotype (OR = 0.516, chi(2) = 4.613, P = 0.032) in the NSCLC patients, compared to controls. The frequencies of AA, AG and GG genotypes did not differ in the NSCLC patients according to the number of pack-years smoked. Based on these results, we suggest that the MCP-1 -2518A/G polymorphism is associated with genetic susceptibility to NSCLC.