The clinical symptoms, measurements of pulmonary function and interpretations of thoracic roentgenograms in 18 patients with .alpha.1-antitrypsin deficiency associated with the PiZ phenotype were 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 having 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 non-smoking persons are variable and suggested that other factors, in addition to phenotype and environmental pollutants, are determinants of the chronic obstructive pulmonary disease. Many of these patients lived in their 6th and 7th decades, suggesting 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.