Following a review of the literature on resistance to Fasciola hepatica, a series of experiments are described, which were designed to study the protective effect of curtailed previous infections, implantation with adult flukes and passive transfer of immune serum in rats and rabbits. Rats were chosen to represent those mammals which readily acquire resistance to F, hepatica e.g. cattle, and rabbits to represent those in which the ability to acquire such resistance is questionable e.g. sheep. One mature or two immature infections which had been eliminated with deacetylated diamphenethide stimulated similar levels of resistance to challenge with F. hepatica. in rats, although the latter procedure resulted in more severe hepatic lesions than the former. In both cases the resistance was manifested by a significant decrease in the numbers of flukes recovered from previously infected rats compared with previously uninfected rats. Following challenge infections, the resistant rats also showed significantly lower mean peak eosinophil counts and significantly lower mean peak glutamic dehydrogenase levels, indicating less liver damage. Higher antibody titres were also recorded after challenge in the previously infected animals than in the controls. On the other hand, in rabbits neither a single mature or two previous immature infections which had been eliminated with rafoxanide stimulated a significant resistance to challenge. - The two previous infections appeared to result in some decrease in the challenge infection but this was not statistically significant and was attributed to structural changes in the liver acting as a mechanical barrier to the development of the chairenge infection. Although such structural changes resulting from previous infections may also play a role in resistance to F. hepatica in rats, the involvement of immunological factors in this resistance was clearly demonstrated by implanting adult flukes subcutaneously or intraperitoneally thus by-passing the parenchymal intrahepatic migration which is the probable stimulus resulting in the mechanical barrier. These implantations resulted in a significant resistance to challenge in rats but not in rabbits. Once again, the resistance was manifested by both a significant reduction of the challenge infection and a significant decrease in the mean peak serum glutamic dehydrogenase levels after challenge. In rats metabolic products diffusing from mature flukes which had been encapsulated in diffusion chambers and implanted subcutaneously or intraperitoneally were found to contain immunogens which stimulated resistance to challenge. Hence, the fluke tegumental cells or the eggs do not appear to have an essential role in this resistance. The similar stimulation of resistance by subcutaneous implantation of one or two encapsulated adult flukes, which were removed after two weeks, showed that the continuing presence of the sensitising flukes was not needed to maintain the resistance, at least in the short term. It was also shown that resistance can be transferred passively by the globulin fraction of serum and therefore probably by antibody. This protective agent in immune serum or immune-gamma globulin could be inactivated or absorbed out by factor(s) present in the metabolic products of cultured flukes. The successful transfer of resistance by immune serum seems to depend on the volume of serum transferred, the time of transfer in relation to infection and the species of the recipient and the donor. Thus immune rat serum or gammaglobulin precipitated from such serum, transferred at the time of challenge and again 2 days later, resulted in a significant level of resistance in terms of both the number of flukes recovered from the challenge infection and the serum glutamic dehydrogenase levels. However such resistance was not obtained in rabbits injected with immune homologous serum. The ratio of the transferred serum to recepienfs weight was about 1:50 in rabbits compared to 1:15 in rats. However, using these same ratios immune rat serum was found to confer protection on rabbits and immune rabbit serum was protective to rats. This suggests that the immune rat serum simply has a greater protective capacity. A similar high protective capacity was also shown by immune bovine serum and by gamma-globulin precipitated from such serum but not by ovine serum. The dissertation ends with a discussion of these results and of their relevance to the various hypotheses which have been advanced to explain the mechanism of resistance to Fasciola hepatica.