A C57BL/6 (B6) methylcholanthrene-induced solid tumor grows progressively in BALB/c mice. The BALB/c mice fail to develop in their spleens cytotoxic lymphocytes directed against the histocompatibility (H-) antigens of the tumor. A B6 skin graft is rejected normally by mice with the progressively growing B6 tumor and skin graft rejection has no influence on the growth of the tumor. Tissue culture-carried tumor cells work satisfactorily as target cells in a 51Cr release assay with effector lymphocytes immunized against B6 H-antigens, but the tumor cells will not work as an immunogen for H-antigens for an in vitro immunization. "Fresh" tumor cells removed from their in vivo environment and separated on a discontinuous bovine serum albumin gradient also work as target cells. The conclusion is drawn that the host cytotoxic lymphocyte response against the tumor, as defined by a short-term 51Cr release assay, suffers from both sensitization and effector stage defects that probably do not involve serum factors or suppressor cells.