Epidemiologic studies show that 5-12% of subjects with chronic obstructive pulmonary disease (COPD) are nonsmokers. Little is known about the pathophysiology of the fixed airflow obstruction in these subjects. We have prospectively identified 25 patients with COPD who had never smoked or had a less than 5 pack years smoking history and present the clinical, radiologic, and induced sputum features. Our population represented 5.7% of total referrals with fixed airflow obstruction over 2 years. Patients had a mean age of 70 years, were predominantly female (86%), and had a mean duration of respiratory symptoms of 7 years. The mean FEV(1) was 58%, and the FEV(1)/FVC was 55%. Features on high-resolution computed tomographic scanning were nonspecific and were considered typical of a wider population with COPD. An induced sputum differential inflammatory cell count suggested the presence of two distinct groups. Nine had significant sputum eosinophilia (mean, 8.1%; normal, less than 1.9%), and the remaining 13 had a normal sputum eosinophil and tended to have a raised sputum neutrophil count (mean, 70.1%; normal, less than 65%). Organ-specific autoimmune disease was present in 7 of the 22 patients (32%) and was particularly prevalent in those without sputum eosinophilia (6 of 13). In conclusion, COPD in nonsmokers predominantly affects females and has at least two pathologic subgroups, one of which may be associated with organ-specific autoimmune disease. Further investigation of this group may disclose novel mechanisms of fixed airflow obstruction.