The cross-reactive idiotype (Hu-SJ-CRIM) is defined by polyclonal human anti-idiotypic antibodies derived from chronically S. japonicum infected patients. The present study shows that serum levels of Hu-SJ-CRIM expressed by antibodies to S. japonicum soluble egg antigen (SEA) are associated with acute infection and hepatosplenic disease. Xenogeneic anti-idiotypic antisera (anti-Hu-SJ-CRIM) suppressed human lymphocyte blastogenesis to SEA in vitro by 47-82% (P < 0.05). These anti-idiotypic antibodies also suppressed in vitro granuloma formation induced by SEA coated heads in a dose dependent manner. This immunosuppression was antigen specific in that mitogen (PHA) or non-related antigen (PPD) induced blastogenic responses were not suppressed. Surprisingly, anti-idiotypic antibodies (anti-SJ-CRIM), which describe the mouse correlate CRIM were not suppressive in the human blastogenesis or in vitro granuloma formation assays. These data indicate a dichotomy in the function and specificity of the idiotype/anti-idiotype human and murine immune networks in S. japonicum infection. Thus, only the patient derived molecules and serology form the basis for an immunoregulatory network in Schistosomiasis japonica.