We examined the proteinase-antiproteinase balance in the bronchoalveolar lavage (BAL) fluid from alpha-1-proteinase inhibitor (alpha 1PI)-deficient lung transplant recipients to determine whether they would derive benefit from intravenous augmentation therapy with alpha 1PI. BAL fluid from 11 alpha 1PI-deficient lung transplant recipients and eight control subjects was assayed for free neutrophil elastase activity, immunoreactive alpha 1PI, and elastase inhibitory capacity. Samples were obtained during intervals of health and respiratory illness. BAL fluid from healthy alpha 1PI-deficient lung transplant recipients had minimal or unmeasurable free elastase activity, which was not different from that of control subjects. alpha 1PI concentrations in BAL fluid from alpha 1PI-deficient lung transplant recipients were reduced when compared with those of control subjects. Despite this observation, all but one alpha 1PI-deficient patient had the ability to inhibit exogenous elastase. During respiratory illness, however, three of seven alpha 1PI-deficient lung transplant recipients had measurable free elastase activity, which was inhibited ex vivo by addition of alpha 1PI. We conclude that alpha 1PI-deficient lung transplant recipients demonstrate free elastase activity in BAL fluid during severe lower respiratory tract inflammation, which is not present during health. Intravenous supplementation of alpha 1PI-deficient lung transplant recipients with exogenous alpha 1PI during respiratory tract inflammation may be indicated to inhibit elastase-mediated injury to the transplanted lung.