Fasciolosis, caused by trematodes of the genus Fasciola, is one of the most important diseases of farmed ruminants in temperate and tropical zones. The appearance of Fasciola hepatica populations that are resistant to common flukicidal drugs means that new methods of treatment will soon be required. The future prospect for the development of anti-liver fluke vaccines is optimistic and given their consumer acceptability and environmental friendliness, offer the best way forward. Cathepsin L proteases (Fhe CL 1 and Fhe CL 2), secreted by liver flukes at all stages of their development in the mammalian host, are believed to play important roles in facilitating parasite migration (tissue degradation), feeding and immuno-evasion. The authors consider them prime targets for which new vaccines can be developed. Vaccine studies in cattle and sheep have shown that protection levels of up to 72 and 79 per cent, respectively, can be obtained with immunisations of cathepsin Ls in Freunds' adjuvant. The vaccine also exhibited high anti-embryonation/anti-fecundity effects on parasites that survived in vaccinated animals and thus could have a major impact on the transmission of disease to the intermediate host. While natural infections in sheep and cattle appear to elicit non-protective Th2 immune responses, the authors' studies indicate that the protection induced by vaccination involves elements of a Th1 response. Copyright 2001 Harcourt Publishers Ltd.