Two recombinant plasmids pVAX/Sj26GST and pVAX/mIL-18 containing Schistosoma japonicum 26kDa GST and murine IL-18 were evaluated for their ability to protect mice against S. japonicum challenge. Mice were given 2 intramuscular immunizations 3 weeks apart, and challenged with S. japonicum cercariae 4 weeks later. Adult worm and egg burdens were determined 48 days post-challenge. All animals vaccinated with pVAX/Sj26GST alone or with pVAX/mIL-18 developed specific anti-SWAP (soluble worm antigen preparation) ELISA antibody and splenocyte proliferation response. Co-injection of pVAX/mIL-18 significantly increased the production of IFN-gamma and IL-12, indicating that IL-18 enhances the Th1-dominant immune response. Challenge experiments showed that worms were reduced in the pVAX/Sj26GST group by 30.1% and by 49.4% in animals given pVAX/mIL-18 additionally. Corresponding hepatic and fecal egg reductions were 44.8% and 53.0%, and 50.6% and 56.6%, respectively. These results indicate that IL-18 may be an effective adjuvant for a schistosomiasis vaccine.