Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease.