Viral hemorrhagic septicemia virus (VHSV) has been found in fish populations throughout the Great Lakes basin since 2003. It is a single-stranded RNA virus that affects a number of fish species, including muskellunge (Esox masquinongy) a major predator in these waters. The purpose of this experiment was to compare the virulence of four strains of VHSV IVb (MI03, vcG002, FPL2013-002 and FLP20140991). Age-0 muskellunge were randomly assigned to one of the strains and exposed to either a high (5 x 105 plaque forming units/mL) or low (5 x 104 plaque forming units/mL) dose for one hour by immersion. Fish were then monitored for clinical signs of infection, such as petechial hemorrhages, lethargy and death, whereupon brain and pooled organ samples were harvested using aseptic technique. Quantitative reverse transcription polymerase chain reaction assays in muskellunge were performed along with viral isolation in order to confirm the presence of HVSV. Results of the Cox proportional hazard regression models did demonstrate a difference when comparing the time to death of the high dose versus the low dose, but no difference was observed when comparing the time to death of the four isolates over the course of the experiment. When comparing viral load in muskellunge pooled spleen, hear, liver and anterior and posterior kidneys or separate brain, there were no differences between the strains or the doses detected. Future studies with lower doses closer to the LD50 may differentiate changes in virulence properties of VHSV IVb.