A 200-kDa protein of the African schistosome Schistosoma mansoni has been identified as a target of antibodies that act in synergy with praziquantel. Treatment of worms with praziquantel exposes selective epitopes of the 200-kDa protein on the surface of S. mansoni and transfer of a monoclonal antibody recognizing the 200-kDa protein at the time of drug treatment restores the effectiveness of praziquantel against infections in B-cell-depleted mice. In the present study, a cross-reactive 200-kDa protein was identified in the three major schistosome species by Western blot analysis using a polyclonal rabbit antiserum recognizing the 200-kDa protein from S. mansoni. Surprisingly, three monoclonal antibodies generated against immunogenic epitopes of the 200-kDa protein did not recognize the 200-kDa protein of the Oriental species Schistosoma japonicum, although they did recognize the 200-kDa protein of another African species Schistosoma haematobium. Furthermore, in the case of S. japonicum, treatment with praziquantel did not expose the 200-kDa protein on the worm surface. Even acetone treatment, which makes surface epitopes more accessible, did not expose the 200-kDa protein on the surface of S. japonicum. In contrast, the 200-kDa protein of S. haematobium was exposed following treatment with praziquantel, and acetone fixation resulted in significantly increased reactivity of the rabbit a200-kDa antiserum with the surface of both S. mansoni and S. haematobium worms.