The S-layer protein and extracellular proteases and hemolysin of the motile aeromonads may play a role in virulence during epizootics of Motile Aeromonad Septicemia (MAS). The objective of the present study was to determine the humoral response of channel catfish to these potential virulence factors. The sera from test fish, survivors of MAS epizootics in commercial channel catfish ponds, were compared to the sera from control fish. For this study, commercially raised catfish that had not experienced a reported outbreak of MAS, and laboratory fish vaccinated with the crude preparation of each virulence factor were used for controls. Sera from the test fish and control fish were used in agglutination assays and western blots. The humoral responses to whole cell antigens and specific virulence factors were recorded.