Eglin-c, a compound that inhibits rat elastase but has little effect on porcine pancreatic elastase (PPE), was employed to examine the role of endogenous elastase in PPE-induced emphysema. Twenty-four female Long-Evans rats were divided into three groups: control (n = 8), PPE (n = 9), and PPE + eglin-c (n = 7). Eglin-c (9 mg/rat) was intratracheally instilled 3 days after PPE treatment, twice weekly, until 3 days before pulmonary function testing. Function tests and lung fixation for morphometric analysis were carried out 15-34 days after PPE treatment. Intratracheal instillation of PPE (400 IU/kg) produced significant increases in functional residual capacity, dynamic and quasi-static compliances, total lung capacity (TLC), and mean linear intercept (MLI), as well as a significant decrease in carbon monoxide diffusion coefficient. However, no significant alterations in quasi-static compliance, TLC, or MLI were found in animals treated with PPE and eglin-c. Three additional groups were used to examine the effects of intratracheal instillation of saline or eglin-c: control (n = 9), saline (n = 8), and eglin-c (n = 10). No significant change in any respiratory parameter was found in either the saline or the eglin-c group, indicating no detectable alteration in pulmonary function caused by either the intratracheal procedure or eglin-c. These data suggest that endogenous elastase is an important contributing factor in the development of PPE-induced emphysema in the rat.