The efficacy of florfenicol for control of mortality associated with Edwardsiella icatluri was studied in fingerlings of Channel Catfish Ictalurus puntatus (Delta strain), Blue Catfish I. furcatus (D&B strain), and a hybrid catfish (Delta strain Channel Catfish × D&B strain Blue Catfish). On day 0, fish were immersion challenged in 65-L aquaria. For each of the three species of catfish, 10 aquaria were randomly assigned to two treatment groups, either treated with florfenicol at 0 mg/kg of body weight (unmedicated feed) or at 10 mg/kg (medicated feed). Fish were treated for 10 consecutive days, monitored for mortality during this treatment period, and observed for 14 d afterwards. Post observation, all survivors were humanely euthanized in tricaine methanesulfonate, cultured for E. ictaluri, and examined for gross pathology. The mean cumulative percent mortality from enteric septicemia of catfish (ESC) challenge among the three genotypes of catfish did not differ between Blue Catfish, hybrid, and Channel Catfish in treated or control groups. However, the florfenicol-treated fish had a significantly lower mean cumulative mortality (6%) than the controls (78%). All genotypes of catfish tested were responsive to treatment with florfenicol-medicated feed for control of mortality associated with ESC. There were no significant differences in mortality associated with hybrid catfish, blue catfish, and Channel Catfish (Delta strain).