We evaluated the susceptibility of Rio Grande cutthroat trout (RGCT) Oncorhynchus clarkii virginalis to infection by Myxobolus cerebralis in a laboratory experiment. In the same experiment, rainbow trout (RBT) O. mykiss were similarly exposed to M. cerebralis as a reference of known sensitivity to the parasite. Treatments consisting of six parasite concentrations (0, 50, 100, 250, 500, and 1,000 triactinomyxons [TAMS] per fish) were randomized within a complete block design using RGCT and RBT fry beginning at 60 d posthatch (600 degree-days at 10??C). The laboratory experiment was terminated at 130 d postexposure (1,900 degree-days at 10??C). Diagnostic metrics included clinical signs (behavioral and black tail), survival, myxospore counts, histology, and a swimming performance challenge. Clinical signs of whirling disease were observed within both species at 500 and 1,000 TAMs/fish by 66 d postexposure to the disease. Rio Grande cutthroat trout exhibited significantly lower survival (50% cumulative mortality at 1,000 TAMs/fish) and a significant concentration response compared with RBT (8% cumulative mortality at 1,000 TAMs/fish). Histological scoring of cranial sections using a 0-5 scale of increasing pathogenic effect revealed greater disease severity in RGCT (3.20) than in RBT (2.43) at 100 TAMs/fish but no difference at 1,000 TAMs/fish (4.15 and 4.12, respectively). Swimming performance revealed detectably lower critical swimming speed in both RGCT and RBT in relation to increased parasite concentrations, the RGCT exhibiting detectably lower critical swimming speeds than the RBT at increased parasite concentration. If M. cerebralis were to spread to areas supporting RGCT, population-level effects may occur. ?? Copyright by the American Fisheries Society 2007.