The guinea pig was used to study the pathology of Fascioloides magna, an important pathogen for sheep. Although flukes migrated freely through various tissues in infected guinea pigs, the most serious lesions occurred in the liver and lungs. The sequential development of lesions indicated that flukes first invaded the quadrate lobe of the liver and subsequently migrated to other liver lobes and tissues. Six weeks post-infection, there was a marked drop in the recovery o[' flukes from the liver along with a dramatic increase in pulmonary involvement. Much of the hepatic and pulmonary pathology in infected animals was secondary to extensive vascular lesions caused by migrating flukes. In the liver, vascular lesions predominantly involved the portal and hepatic veins. Thrombophlebitis and locally extensive necrosis, resembling infarction, were observed. Vascular lesions in the lungs occurred in the pulmonary arteries leading to thrombosis and haemorrhagic infarction. Discovery of a fluke in a pulmonary artery, along with the pattern of hepatic and pulmonary lesions, suggested that flukes probably used the cardiovascular system as a pathway for dissemination. Death in fluke-infested guinea pigs was most often associated with severe pulmonary lesions. The nature and distribution of fluke-induced lesions observed in this study demonstrate that the guinea pig is a suitable animal model for Fascioloides magna infection in sheep.