The hematologic and clinico-pathologic response to Fascioloides magna infection in cattle and guinea pigs was investigated. Twelve calves (six infected and six controls) were monitored for 26 weeks after inoculation with 1000 metacercariae. All calves remained healthy and there were no significant differences in weight gains between infected and control groups. Flukes (mean = 9.2, range 1-32) were recovered from the liver and abdominal cavity of all infected calves. The only significant response observed in the complete blood counts was an eosinophilia present in the infected calves extending from Weeks 2 to 26 post-infection. There were no significant differences in serum levels of aspartate aminotransferase and only minor increases in the levels of gamma-glutamyl transferase and sorbitol dehydrogenase. A total of 48 infected and 48 control guinea pigs from three separate experiments were monitored for 16 weeks after inoculation with 20 metacercariae of Fascioloides magna. Infected guinea pigs died between 7 and 114 days after infection, and flukes (ean = 2.5, range 0-13) were recovered from the liver, abdominal cavity, lungs, thoracic cavity, skeletal muscle and subcutaneous tissue. There were no differences in weight gains between infected and control guinea pigs. Complete blood counts showed increases in white blood cell, monocyte and neutrophil counts from between the third and fourteenth weeks post-infection; however, the differences were not consistently significant. Infected guinea pigs developed a significant eosinophilia and basophilia from 2 to 16 weeks post-infection. There were no significant changes in the serum levels of alanine aminotransferase or gamma-glutamyl transferase. There was an increase in the serum levels of aspartate aminotransferase beginning at 5 weeks post-infection. The response observed in the guinea pigs was similar to that reported in sheep, suggesting the suitability of the guinea pig as a model for Fascioloides magna infection in the sheep.