Tumour necrosis factor(TNF)-alpha levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-alpha gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians. Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood. There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung). It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease.