2-Trifluoroacetamidobenzenesulfonyl fluoride was shown to be a potent inhibitor of porcine pancreatic elastase activity with an ID50-30.3 microM. When this enzyme was infused I.V. in mice inducing higher elastase activity in the blood, the agent at 20 mg/kg for 5 days suppressed elastase activity significantly below the value observed in normal mice. The drug was absorbed better by the I.P. route than the P.O. route. A more consistent and higher blood level of the drug was achieved by the I.P. route as opposed to the I.V. or oral routes. The drug distributed rapidly to all tissues concentrating in the skin and carcass. Approximately 56% of the drug was eliminated within 48 hr. The majority of the eliminated drug and its metabolites was via the urine. Whereas the LD50 value was greater than 350 mg/kg I.P. there was elevation in serum alkaline phosphotase activity; cholesterol and triglyceride levels were reduced, and the organ weight of the reproductive organs was markedly reduced. Further evaluation of this drug is necessary to determine if the observed acute toxicity findings are restrictive for the use of this agent in the treatment of emphysema.