We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients.