Eighteen-year-old adolescents with α 1-antitrypsin (α 1 AT) deficiency have mostly normal lung function tests. We hypothesized that compensatory increases in other protease inhibitors and/or a decreased leukocyte activity might favorably affect the protease/protease-inhibitor balance in α 1 AT-deficient adolescents. At the age of 18 y 46 PiZZ (severe deficiency), 22 PiSZ (moderate deficiency), and 41 control subjects were studied. The plasma protease inhibitors α 2-macroglobulin (α 2 M), α 1-antichymotrypsin (Achy), and secretory leukocyte protease inhibitor (SLPI) were studied, and the protease elastase complexed with α 1 AT (HEAT) and neutrophil gelatinase-associated lipocalin (NGAL) as indicators of neutrophil leukocyte activity. Significantly higher concentrations of α 2 M were found in PiZ (p< 0.0001) and PiSZ (p< 0.0001) individuals compared with control subjects. The PiZZ and SZ adolescents had low levels of NGAL (p< 0.0001). Low levels of HEAT were found in PiZZ subjects (p< 0.0005). Higher concentrations of Achy were found in PiZZ (p< 0.04) and PiSZ (p< 0.05) individuals. Increased concentrations of α 2 M and Achy combined with decreased levels of HEAT and NGAL, indicating decreased leukocyte activity may, to some extent, compensate for the protease/protease inhibitor imbalance in the α 1 AT-deficiency state.