Mechanisms of resistance have been studied by several authors in different animal species. These studies may help to better understand the immune response to "F. hepatica" in host and are necessary in development of vaccine against the parasite. It has been established that cattle acquire resistance to challenge infection with "F. hepatica" and "F. gigantica" when they have been sensitized with primary patent or drug-abbreviated infection. Resistance to fasciolosis was also documented in rats. On the other hand, sheep and goats are not resistant to re-infection with "F. hepatica". However, there is evidence that two sheep breeds, in particular Indonesian thin tail sheep and Red maasai sheep, are resistant to "F. gigantica". No reports concerning the resistance in humans are available.

Human "F. hepatica" infection is determined by the presence of the intermediate snail hosts, domestic herbivorous animals, climatic conditions and the dietary habits of man. Sheep, goats and cattle are considered the predominant animal reservoirs. While other animals can be infected, they are usually not very important for human disease transmission. On the other hand, some authors have observed that donkeys and pigs contribute to disease transmission in Bolivia. Among wild animals, it has been demonstrated that the peridomestic rat ("Rattus rattus") may play an important role in the spread as well as in the transmission of the parasite in Corsica. In France, nutria ("Myocastor coypus") was confirmed as a wild reservoir host of "F. hepatica". Humans are infected by ingestion of aquatic plants that contain the infectious cercariae. Several species of aquatic vegetables are known as a vehicle of human infection. In Europe, "Nasturtium officinale" (common watercress), "Nasturtium silvestris", "Rorippa amphibia" (wild watercress), "Taraxacum dens leonis" (dandelion leaves), "Valerianella olitoria" (lamb's lettuce), and "Mentha viridis" (spearmint) were reported as a source of human infections. In the Northern Bolivian Altiplano, some authors suggested that several aquatic plants such as bero-bero (watercress), algas (algae), kjosco and tortora could act as a source of infection for humans. Because "F. hepatica" cercariae also encyst on water surface, humans can be infected by drinking of fresh untreated water containing cercariae. In addition, an experimental study suggested that humans consuming raw liver dishes from fresh livers infected with juvenile flukes could become infected.