The majority of deaths in severe pancreatitis are the result of superinfection of necrotic tissue. The pathogen most commonly responsible for such infections is Escherichia coli. Antibiotic prophylaxis would appear a logical precaution. The antibacterial drugs of choice should possess two basic characteristics: they must be active against the flora responsible for the infections and must be capable of penetrating into the pancreas at adequate minimum inhibitory concentrations (MICs). Mezlocillin--which is active against E. coli--has been shown to possess the latter requisite, but achieving therapeutic concentrations requires administration at high doses. In the present study, pure human pancreatic fluid showed properties similar to those observed in the dog against E. coli (bacterial colony growth 100 times lower than in a control culture) and produced a 75% reduction in mezlocillin MICs against this organism. These enhancing characteristics might make the commonly used doses sufficient for prophylactic purposes.