Various autoantibodies to nuclear antigens were detected by ELISA in pooled sera of 15 ICR mice 9 weeks after infection with schistosoma. The binding of this serum with acute infection to cercarial extract was inhibited by prior incubation of the sera with DNA, polynucleotides and cercarial extract. Sera from 9 BALB/c mice with experimentally induced lupus, reacted with cercarial extract. No binding was noted with normal mouse sera (NMS). Similarly, sera of SLE patients (N = 113) reacted with the parasite extracts in a higher incidence (14.2%) compared to NHS (3.7%) (P < 0.05). Immunoblot analysis showed common features to SLE sera reacting with two antigenic "groups". The first are antigens that also were recognized by sera of mice infected with schistosomiasis (60, 85, and 94 kDa cercarial proteins). The second group entailed proteins that bound with SLE sera only (10-18 kDa, 29 kDa and 52 kDa). It can be concluded that antinuclear autoantibodies can be found in sera of acute infected mice with schistosomiasis, while SLE sera may react with 3 schistosomal extracts in a higher incidence than NHS (P < 0.05). These results suggest an autoimmune response in schistosomiasis. It is possible that a parasite infection (as bilharzia) may be one of the "trigger" mechanisms for SLE in a subject with the suitable immunogenetic and hormonal background.