We describe an injection model for creating furunculosis, caused by Aeromonas salmonicida, in seawater-adapted Atlantic salmon Salnw salar and for testing the efficacy of chemotherapeutants. An injection model was most appropriate for chemotherapcutant studies. Isolate selection was based on determination of drug resistance and the pathogenicity of the isolate, both of which can vary widely. Fish were handled without anesthesia with minimal handling stress; their feeding behavior was normal. Preliminary challenge trials demonstrated highly variable pathogenicity for different isolates of A. salmonicida. In the main four-dose challenge of 30. 90. 300, and 900 bacteria per fish, cumulative 16-d mortality rates ranged from 28% to 38%. Onset of deaths was earlier for the two higher doses, and these doses resulted in greater cumulative mortality than did the lower two doses. Power analysis of the data showed that with a tive-replicale study, a 12.1% difference in cumulative mortality rate between the control and treatment would be required to show statistical significance at the P = 0.05 level and that with four-, three-, and two-replicate studies, cumulative mortality rate differences between treatment and control of 13.6%, 15.7%, and 19.1%, respectively, would be required. The data generated can be used to define the parameters for definitive challenges used to establish drug dose-efficacy relationships.