In an effort to determine the mechanism of papain action in causing an emphysema-like lesion in hamsters, the number and types of cells and the activities of two lysosomal enzymes in the lung were determined after papain exposure. Three and four weeks after a 3-h exposure to an aerosol of 3% papain the following alterations in lung structure and function were observed: (1) the mean linear intercept, or average distance between adjacent alveoli, was increased; (2) the internal surface area declined; (3) the dynamic compliance was elevated at low breathing frequencies. The numbers of cells present free in the lung increased from a control value of 2.0 +/- 0.2 x 10 (6) to 6.6 +/- 0.5 x 10 (6) 5 days after exposure. The free beta-glucuronidase, alysosomal enzyme, likewise increased over threefold during the first 3 days after exposure. These results are consistent with the hypothesis that papain induces an inflammatory-type responses, and this may be in part responsible for inducing the lesion.