Antibodies to Schistosoma mansoni soluble egg antigens (SEA) generated in outbred rabbits from two different sources were used to study cross-reactive idiotype/anti-idiotype (Id/anti-Id) interactions in S. mansoni-infected mice in two different locations. Immunoaffinity purified rabbit polyclonal anti-SEA antibody preparations (RabId) were predominantly Ig by SDS-PAGE and demonstrated anti-SEA activity by ELISA and Western blot. RabId prepared from three separate rabbits and used at 40 micrograms/ml in vitro stimulated lymphocyte proliferative responses of spleen cells from mice with eight week infections (Mean +/- SEM [E-C]) of 3869 +/- 764, 18594 +/- 3046 and 8962 +/- 1734 cpm. Spleen cells from uninfected mice exposed to the same RabId preparations in vitro had respective [E-C] values of 206 +/- 144, 494 +/- 154 and 363 +/- 180. Lymph node cells from mice infected for 8 weeks demonstrated [E-C] of 123 +/- 400, 5073 +/- 828 and 2361 +/- 656 upon exposure to these 3 RabId preparations. Lymph node cells from uninfected mice had [E-C] of 220 +/- 76, 194 +/- 82 and 143 +/- 72 when exposed to these RabId. Maximum in vitro proliferative response to Ig from unimmunized rabbits was 761 +/- 400 by spleen cells from mice with eight week infections. These data indicate the presence of cross-reactive Id on rabbit anti-SEA antibodies from different rabbits that can stimulate in vitro lymphoproliferative responses of spleen or lymph node cells from S. mansoni-infected mice.