Although several species of Tetrahymena are often described as histophagous and opportunistic pathogens of fish, little is known about ciliate/fish cell interactions, but one approach for studying these is in vitro with cell lines. In this study, T. thermophila, B1975 (wild type) and NP1 (temperature sensitive mutant for phagocytosis) were cultured on monolayers of 3 fish epithelial cell lines, CHSE-214, RTgill-W1, and ZEB2J, and the rabbit kidney epithelial cell line, RK-13. Generally the ciliates flourished, whereas the monolayers died, being completely consumed over several days. The destruction of monolayers required that the ciliates could make contact with the animal cells through swimming, which appeared to dislodge or loosen cells so that they could be phagocytosed. The ciliates internalized into food vacuoles ZEB2J from cell monolayers as well as from cell suspensions. Phagocytosis was essential for monolayer destruction as monolayers remained intact under conditions where phagocytosis was impeded, such as 37°C for NP1 and 4°C for B1975. Monolayers of fish cells supported the proliferation of ciliates. Thus T. thermophila can ‘eat’ animal cells or be histophagous in vitro, with the potential to be histophagous in vivo.