Cobra venom factor (CoV), treated to remove contaminating phospholipase A(2), was administered to normal hamsters in a manner designed to inactivate their C3. Such treatment was shown to remove all of the hemolytic complement activity in the serum from the treated hamsters. Treated and untreated hamsters were then subjected to LPS 5 h aerosols of E. agglomerans. When lungs of both groups of animals were analyzed morphometrically 6 h after aerosolization, it was found that CoV treatment abrogated LPS induced accumulations of neutrophils and platelets in pulmonary capillaries, but not changes in distal lung volume. A two signal pathogenetic hypothesis is presented which states that although complement activation alone is not responsible for all of the morphomentric changes induced by endotoxin inhalation, it is an important signal required for the process.