Endotoxic shock was induced in rabbits of either sex by IV injection of 50 micrograms/kg endotoxin (ET) extracted from E coli O-55 by Boivin's method. A polyvinyl catheter was introduced into the superior vena cava under local anesthesia 1 day prior to the experiments. We observed a rise of plasma-free fatty acids (FFA) from an initial mean value of 190 muEq/liter to a level of 290 muEq/liter within 6 h after injection of endotoxin. The increase of FFA was followed by a rise of plasma triglycerides (TG) and an increase of very low-density lipoproteins (VLDL), beginning 1-2 h later. The rise of FFA and the following increase of TG and VLDL were significantly reduced by infusion of 14 micrograms/kg X min gabexate mesilate (GM). Our results indicate that GM--in addition to its well-known proteinase inhibitory action--effects fatty acid metabolism.