Cigarette smokers have an increased risk of chronic obstructive airways disease which has been attributed to a protease-antiprotease imbalance in the lung. The neutrophil is an important source of proteases as well as of myeloperoxidase, which oxidatively inactivates alpha-1-proteinase inhibitor (alpha-1-PI). The purpose of this study is to evaluate the protease-antiprotease imbalance hypothesis by measuring changes in peripheral blood components in a group of 110 young, male, asymptomatic smokers and an equal number of age-matched non-smokers. Significant (p = 0.001), but modest impairment of pulmonary function was observed in the smokers as measured by both forced expiratory spirometry and the single breath nitrogen test. A 35% increase (p = 0.0001) in peripheral blood leukocytes in smokers was attributable to increases in neutrophils (44%), lymphocytes (31%) and monocytes (23%). This increase in leukocyte count correlated significantly (p less than or equal to 0.01) with some of the more sensitive indicators of airway obstruction (FEV1/FVC, CV/VC, CC/TLC, and delta N2/L). Myeloperoxidase activity of neutrophils isolated from peripheral blood of smokers was 13% higher than in non-smokers, while elastase activity per neutrophil was apparently unaffected by smoking. In 50 subject pairs, elevations in serum alpha-1-PI concentrations in smokers (13.7%) were comparable to similar increases in trypsin (9.9%) and elastase (12.4%) inhibitory capacities. Expressed as nanomoles protease inhibited per nanomole of alpha-1-PI, the apparent functional activity of alpha-1-PI was unaltered by smoking. However, a lower, apparent functional activity of alpha-1-PI against trypsin and elastase was observed in both smokers and non-smokers with higher serum alpha-1-PI concentrations. Thus, in a population of young smokers, changes in leukocyte count, neutrophil lysosomal enzyme activities, and functional serum antiprotease activity appear to be consistent with the establishment of a protease-antiprotease imbalance. This imbalance may predispose these smokers to obstructive lung disease.