Myxobolus prochilodus and Myxobolus porofilus are parasites of Prochilodus lineatus, an economically important South American fish found in La Plata and Paraiba do Sul river basins. This study focusing on parasite-host interaction provides an ultrastructural and phylogenetic analysis, the latter based on ssrDNA sequencing of these parasites respectively infecting the gill filaments and fins of P. lineatus taken from the Mogi Guaçu River, São Paulo, Brazil. A total of 13 adult specimens were examined in this study. The prevalence of infection was 7.69 % for M. prochilodus and 15.38 % for M. porofilus. Phylogenetic analysis showed M. prochilodus and M. porofilus clustered in a subclade composed of parasites of the Prochilodontidae family. In M. prochilodus infecting gill filaments, where cellular degeneration in the epithelium was observed, the plasmodia were surrounded by a capsule composed of layers of fibrocyte-like cells, with cellular projections joined to the projections of other fibrocyte-like cells by desmosomes, and more externally typical fibroblast layers. Some granular leukocytes were seen interspersed among these layers. In M. porofilus infecting the fins, the capsule of connective tissue was represented only by loosely arranged collagen fibers, and no granular leucocytes were observed. Finally, several unusual vacuoles with filamentous content and some characteristics usually described as degenerative alterations, as myelin figure, were noted in plasmodia and pansporoblasts of both myxosporean species. The possible influence of inflammatory response and xenobiotics was considered to be the explanation for the alterations observed in Myxobolus species and its host.