The authors compared histories of nonmalignant respiratory diseases (asthma, bronchitis, emphysema, hay fever, and pneumonia) in 1,553 lung cancer patients and 1,375 healthy controls enrolled in a Texas case-control study from 1995 to 2003. They incorporated data on two biologically relevant polymorphic genes, matrix metalloproteinase-1 and myeloperoxidase. Emphysema was associated with a statistically significant increased lung cancer risk (odds ratio (OR) = 2.87, 95% confidence interval (CI): 2.20, 3.76), while hay fever had a significant protective effect (OR = 0.58, 95% CI: 0.48, 0.70). Odds ratios were consistent after exclusion of respiratory disease diagnoses made up to 10 years before interview. There was little association between other respiratory diseases and lung cancer risk. Among carriers of "protective" genotypes, emphysema was associated with a 1.7-fold increased risk (95% CI: 0.84, 3.50), as compared with the substantially higher risk for persons possessing one (OR = 4.98, 95% CI: 2.94, 8.44) or two (OR = 4.23, 95% CI: 1.84, 9.73) "adverse" genotypes. For hay fever, significantly decreased risks were evident with one (OR = 0.32, 95% CI: 0.21, 0.50) or two (OR = 0.35, 95% CI: 0.19, 0.66) protective genotypes as compared with none (OR = 0.69, 95% CI: 0.30, 1.59). The biologic role of respiratory disease in lung cancer is unclear. Further study may yield new insights for identification of susceptible subgroups.