The clinical symptoms, measurements of pulmonary function, and interpretations of thoracic roentgenograms in 18 patients with alpha1-antitrypsin deficiency associated with the PiZ phenotype are reported. The patients had never smoked and had little or no exposure to occupational and urban air pollution. The findings were compared with those in a group of patients who also had the PiZ phenotype, but who were smokers. The results showed that the clinical course, rate of pulmonary-function deterioration, and appearance of the thoracic roentgenograms in persons who had never smoked are variable and suggested that other factors, in addition to phenotype and environmental pollutants, are determinants of the chronic obstructive pulmonary disease that develops in these patients. Many of these patients lived into their sixth and seventh decades, suggesting that those patients who avoid respiratory irritants do not necessarily have an ominous prognosis. These are important considerations in the diagnosis and treatment of patients who have this deficiency.