The pig is a natural host of Schistosoma japonicum and a useful animal model of human disease. In the present study mRNA levels of Th1 (IFN-γ) and Th2 (IL-10 and IL-4) cytokines were assessed by RT-PCR within tissues from infected pigs. Twelve Danish crossbred pigs were infected by intramuscular injection or orally with 1000 cercariae. Six other pigs served as non-infected controls. Liver and intestinal tissues were collected 10 weeks post-infection, and analysed for their relative levels of cytokine mRNA. Infected pigs developed a Th2 response as characterized by the increased level of mRNA encoding for IL-4 and IL-10 in their large intestine (caecum and colon). In contrast, levels of IFN-γ did not differ between control and infected animals although variation between animals was observed. When comparing the immune response of orally and intramuscularly infected animals, we found that orally infected pigs produced higher IL-4 and IL-10 levels in their caecum and colon respectively. This stronger Th2 response correlated with a previously reported delay in maturation of infection following oral infection. The cytokine expression levels in tissue samples taken from lesion sites and in nearby areas, without obvious lesions, were then compared. Subsequent to an oral infection, the Th2 type cytokine production was higher in the lesion sites of the liver. In conclusion, this study is the first demonstration of IL-4 and IL-10 cytokine response in pig tissues during S. japonicum infection.