A series of 1,458 consecutive patients referred to the Cleveland Veterans Administration Pulmonary Clinic for pulmonary function studies was evaluated for alpha 1-antitrypsin deficiency by determination of serum trypsin inhibitory capacity (STIC). Protease inhibitor (Pi) phenotyping was performed on all sera with STIC values less than 1.6 mg/ml. The following non-MM phenotypes were found: 1FZ, 32MZ, 2ZZ, 3SZ, 5SS, 33MS, 21M. The prevalence of Pi Z heterozygosity is 2.74%. This figure is not significantly greater than that observed in a healthy population. A group ( n = 12) with heterozygous Z phenotype (MZ + SZ) was compared with a control (MM) group (n = 13) matched for age, race and smoking history from this same population. Our findings indicate similar deviations from predicted normal values in both control (MM) and Z-heterozygotic groups for physiologic tests of airway resistance, lung volumes, diffusing capacity, and static and dynamic compliance. There was no significant difference between MM controls and MZ heterozygotes in the physiologic variables measured.