The introduction of American shad from the Atlantic to the Pacific coast of North America in the late 1800’s and the subsequent population expansion in the 1980’s resulted in the amplification of Ichthyophonus sp., a Mesomycetozoean parasite of wild marine fishes. Sequence analysis of the ribosomal DNA gene complex (small subunit and internal transcribed spacer regions) and Ichthyophonus epidemiological characteristics indicate a low probability that Ichthyophonus was co-introduced with American shad from the Atlantic; rather, Ichthyophonus was likely endemic to marine areas of the Pacific region and amplified by the expanding population of a highly susceptible host species. The migratory life history of shad resulted in the transport of amplified Ichthyophonus from its endemic region in the NE Pacific to the Columbia River watershed. An Ichthyophonus epizootic occurred among American shad in the Columbia River during 2007, when infection prevalence was 72%, and 57% of the infections were scored as moderate or heavy intensities. The epizootic occurred near the record peak of shad biomass in the Columbia River, and corresponded to an influx of 1,595 mt of infected shad tissues into the Columbia River. A high potential for parasite spillback and the establishment of a freshwater Ichthyophonus life cycle in the Columbia River results from currently elevated infection pressures, broad host range, plasticity in Ichthyophonus life history stages, and precedents for establishment of the parasite in other freshwater systems. The results raise questions regarding the risk for sympatric salmonids and the role of Ichthyophonus as a population-limiting factor affecting American shad in the Columbia River.