Objective: To identify determinants of pulmonary function and health-related quality of life (HRQOL) to better understand disease severity in patients with asthma and COPD. Design: Observational study. Setting: Dutch general practice. Patients: We studied 837 asthma patients and 231 COPD patients. Results: The association between pulmonary function and HRQOL was poor for asthma (β = 0.10) and COPD (β 5 0.19). Multivariately, in asthma, lower pulmonary function was associated with male gender, region of living, current smoking, use of inhaled short-acting bronchodilators, longer duration of disease, and higher diurnal variation in peak expiratory flow. In COPD, lower pulmonary function was associated with male gender, use of inhaled bronchodilators, more days and nights disturbed by respiratory complaints, not wheezing, and bronchial hyperresponsiveness. Reduced HRQOL was associated most strongly with more days and nights disturbed by respiratory complaints and dyspnea in both asthma and COPD. In asthma, additional associations were found with younger age, lower educational level, region of living, comorbidity, use of inhaled bronchodilators and corticosteroids, wheezing, chronic cough, sputum production, and bronchial hyperresponsiveness. In COPD, lower age, not smoking, chronic cough, and sputum production were associated with reduced HRQOL. Conclusions: Pulmonary function and HRQOL appear to highlight different aspects of disease severity in asthma and COPD. Therefore, both measures should be taken into account in order to get a complete picture of severity of disease.