Thirty patients with advanced colorectal carcinoma (CRC) were treated with alum-precipitated polyclonal goat anti-idiotypic antibodies (Ab2) to monoclonal anti-CRC antibody CO17-1A (Ab1) in doses between 0.5 and 4 mg per injection. All patients developed anti-anti-idiotypic antibodies (Ab3) with binding specificities on the surfaces of cultured tumor cells similar to the specificity of Ab1. Furthermore, the Ab3 competed with Ab1 for binding to CRC cells. Fractions of Ab3-containing sera obtained after elution of the serum immunoglobulins from CRC cells bound to purified tumor antigen and inhibited binding of Ab2 to Ab1. The Ab3, therefore, may share idiotopes with Ab1. Six patients showed partial clinical remission and seven patients showed arrest of metastases following immunotherapy. Four of the thirteen patients with measurable clinical responses had received Ab2 alone, whereas 9 patients had also received chemotherapy.