We compared the resistance to whirling disease of two groups of Colorado River rainbow trout Oncorhynchus mykiss and a domestic strain of rainbow trout in a controlled laboratory challenge. These three groups represented the progeny of wild rainbow trout known to have recruited (1) during the early years of infestation by Myxobolus cerebralis of the Colorado River or (2) before the presence of M. cerebralis in the system and (3) the Erwin strain of rainbow trout. The severity of whirling disease in each group was dependent on the dose of triactinomyxons of M. cerebralis to which the fish were exposed. Microscopic lesions and spore counts both increased with increasing parasite dose. Survival of the progeny of Colorado fish that recruited before the presence of M. cerebralis in the system was significantly less than was that of the domestic fish exposed to 0 and 1,000 triactinomyxons/fish. The parents that recruited to the system before the presence of M. cerebralis were considerably older than were those used for our domestic strain; this difference in parent age probably resulted in the difference in survival because egg quality decreases with age in rainbow trout. There was no difference in microscopic lesions, spore counts, or swimming performance among the three groups of rainbow trout when exposed at the same parasite level, indicating that there was no difference in resistance to whirling disease among these groups of fish.