Technical Abstract: Differences in bacterial loads, clearance rates, and cortisol response were measured for ESC-susceptible and resistant channel catfish families following immersion challenge. The quantity of E. ictaluri DNA present in blood, anterior kidney, and spleen samples from individual fish was compared for 3 ESC-susceptible and 3 ESC-resistant families of catfish. Fish from resistant families had increased survivorship during the challenge when compared to susceptible families. Bacterial loads were higher in susceptible families than for resistant families in blood, anterior kidney, and spleen tissues following exposure to E. ictaluri. Mean quantities of bacterial cell equivalents (log) per 100 uL of blood at 5 days post-exposure were 4.53 ± 0.22 for the susceptible families and 1.79 ± 0.25 for the resistant families. Blood, kidney, and spleen bacterial levels were highly correlated. Pathogen clearance was evident by day 12 in fish from the susceptible families and not measurable in resistant families. An acute stress response was evident for both resistant (21.4 +/- 1.7 ng/mL) and susceptible families (30.0 +/- 1.6 ng/mL), however overall cortisol response differed between groups. On day 5, cortisol levels were 14.5 +/- 1.1 ng/mL for resistant families and 26.2 +/- 1.4 ng/mL for susceptible families. Plasma cortisol levels were elevated in susceptible fish throughout challenge with the exception of day 12, but recovered to near basal levels immediately after the acute response on day 2 in resistant fish. An early host-response mechanism, such as innate immunity, may be less effective in susceptible families, leading to increased levels of infection and increased stress, as indicated by cortisol levels. It is likely that a non-specific immune response among resistant families was effective during early stages of infection, improving upon the effectiveness of the adaptive response at later stages of infection.