To establish a murine model for the monoclonal anti-idiotype immunotherapy of B cell lymphoma, a panel of rat and murine monoclonal anti-idiotype antibodies of several different isotypes was generated against the surface immunoglobulin of the murine B cell tumor 38C13 (38C). Xenogeneic antibodies were made from fusions of rat spleen cells immunized with the 38C idiotype. Syngeneic monoclonal anti-idiotypes were generated from mice immunized with the idiotype conjugated to the protein carrier KLH. Small differences were noted in the ability of the antibodies to cross-block one another, but all appeared to be directed against the same or closely spaced idiotopes on the immunoglobulin molecule. The antibodies selectively precipitated surface Ig from 38C tumor cells and not from normal mouse spleen cells. They were used to selectively stain 38C tumor cells in cell suspensions for FACS analysis or immunohistochemical staining of tissue sections from mice bearing the tumor. As the malignancy progressed, the number of tumor cells found in all tissues examined increased. Thus, the anti-Id antibodies provided a specific probe for tumor cell detection. The antibodies had no detectable effect on cell growth in vitro; however, they did cause the rapid transient loss of the expression of cell surface Ig. This modulation was concentration and time dependent but not 100% complete. Re-expression of the Id occurred by 24 h following removal of the anti-Id antibodies. When these antibodies were used in sensitive radioisotope and enzyme linked immunoassays, the tumor cells were found to secrete small amounts of idiotype in vitro and in vivo. The level of idiotype detected in vivo correlated with tumor growth and inversely with survival. This work is an attempt to develop further an animal model system in which to test the diagnostic and therapeutic effects of monoclonal anti-idiotype antibodies.