Technical Abstract: A study was performed to compare proteomic profiles of channel catfish from families with high and low susceptibility to Edwardsiella ictaluri following an immersion challenge. Total protein was isolated from head kidney samples, collected at 2 and 6 hours post exposure, and analyzed by 2-D-gel electrophoresis coupled with peptide mass fingerprint analysis by matrix-assisted laser desorption/ionization and time of flight tandem mass spectrometry. Comparisons were made between proteomic profiles from infected and uninfected fish from high and low susceptibility families. Heat shock protein 90-beta, from the high susceptibility infected family, and fructose-1, 6-bisphosphatase 1-like protein, from the low susceptibility infected family, were identified at 2 hours post-exposure. RAB-11-like protein (low susceptibility infected family), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (low susceptibility infected family), glyceraldehyde-3-phosphate dehydrogenase (high susceptibility infected family), and ATP synthase beta subunit (low susceptibility uninfected family) were identified at 6 hours post-exposure. Four proteins, heat shock protein 90-beta, RAB-11, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, and glyceraldehyde-3-phosphate dehydrogenase, have activities involved in macrophage function or cellular stress responses, while the other two have functions associated with cellular energy production and metabolism. These results demonstrate the potential for use of proteomic techniques in channel catfish research.