Immunotherapy with monoclonal antibodies has become a hopeful approach to the adjuvant therapy of cancer patients. Recently, formation of antiidiotypic antibodies (Ab2) has been demonstrated in ovarian cancer patients after immunization with F(ab')2 fragments of the monoclonal antibody OC 125 (MAb OC 125). Preliminary results suggested that patients with high Ab2 serum concentrations had better survival rates compared to those where low or no Ab2 serum levels were detected. Beginning in 1992, 23 patients with advanced ovarian adenocarcinomas have been treated with repeated intravenous applications of the MAb B72.3, which is directed against the ovarian carcinoma associated antigen TAG-72. Five of them had been pretreated with several F(ab')2 MAb OC 125 infusions. Blood sample analysis revealed a remarkable antiidiotypic antibody (Ab2) response in 14 patients, with five patients developing high serum levels > 1000 U/ml. Ab2 serum concentrations increased with increasing number of Mab B72.3 applications. In terms of serum levels, corresponding antiidiotypic antibody responses in patients who received both the F(ab')2 MAb OC 125 and the MAb B72.3 differed considerably. We conclude that the use of MAb B72.3 may be an additional beneficial approach to the immunological therapy of ovarian cancer. Subsequent MAb B72.3 application after failure of the F(ab')2 MAb OC 125 may induce appreciable Ab2 serum concentrations and vice versa.