RATIONALE: The contribution by asthma to the development of fixed airflow obstruction and the nature of its effect combined with active smoking and atopy remain unclear. OBJECTIVES: To investigate the prevalence and relative influence of lifetime asthma, active smoking and atopy on fixed airflow obstruction in middle-age. METHODS: The population-based Tasmanian Longitudinal Health Study cohort born in 1961 (n=8,583) and studied with pre-bronchodilator spirometry in 1968 was retraced (n=7,312) and resurveyed (n=5,729 responses) from 2002-2005. A sample enriched for asthma and chronic bronchitis underwent a further questionnaire, pre- and post-bronchodilator spirometry (n=1,389), skin prick testing, lung volumes and diffusing capacity measurements. Prevalence estimates were re-weighted for sampling fractions. Multiple linear and logistic regression were used to assess the relevant associations. MEASUREMENTS: Main effects and interactions between lifetime asthma, active smoking and atopy on fixed airflow obstruction. MAIN RESULTS: The prevalence of fixed airflow obstruction was 6.0% (95% confidence interval 4.5%-7.5%). Its association with early-onset current clinical asthma was equivalent to a 33 pack-year history of smoking (odds ratio 3.7 [1.5-9.3] p=0.005), compared to a 24 pack-year history for late-onset current clinical asthma (odds ratio 2.6 [1.03-6.5] p=0.042). An interaction (multiplicative effect) was present between asthma and active smoking on the ratio of post-bronchodilator forced expiratory volume in one second/ forced vital capacity (FEV1/FVC), but only among those with atopic sensitization. CONCLUSIONS: Active smoking and current clinical asthma both contribute substantially to fixed airflow obstruction in middle-age, especially among those with atopy. The interaction between these factors provides another compelling reason for atopic, current asthmatics who smoke to quit.