We have made monoclonal antiidiotypic antibodies (Ab2) relating to the p97 antigen of human melanoma. This was accomplished by immunizing BALB/c mice with 96.5, a monoclonal antibody (MAb) specific for epitope p97a, hybridizing their spleen cells with NS-1 myeloma cells, and selecting for hybridomas making antibody binding to Fab fragments prepared from MAb 96.5 (Fab 96.5). The Ab2 were tested for binding to Fab 96.5, as well as for their ability to inhibit the binding between MAb 96.5 and p97. Three monoclonal Ab2 were identified which competitively inhibited the binding between p97 and MAb 96.5 when injected into either BALB/c or C3H/HeN mice; two of them induced Ab3 which expressed the same idiotype as MAb 96.5 and which were specific for p97. These two Ab2 thus appear to functionally mimic p97. They were, however, unable to induce delayed-type hypersensitivity to p97 and to protect mice against transplants of p97-positive mouse melanoma cells, suggesting that the epitope recognized by MAb 96.5 may not be a target for cell-mediated rejection of tumors.