Murine plasmacytoma MOPC 104E-KI81 is a tissue culture cell line of MOPC 104E derived from BALB/c mice. MOPC 104E-KI81 implanted subcutaneously in syngeneic normal mice regresses spontaneously after an initial growth of about 10 mm. Mice that regressed tumors or mice immunized intraperitoneally with mitomycin C-treated MOPC 104E-KI81 myeloma could reject subsequent challenge of viable KI81 myeloma cells. In contrast to euthymic mice, T-cell-deficient athymic nude mice developed subcutaneous tumors after challenge and died from progressive tumor growth, suggesting the critical role of T cells in tumor regression. In vitro induction of cytotoxic cells was used to define the immunologic mechanism by which the host can suppress tumor growth. Spleen cells from immune mice did not show cytolytic activity in 51Cr release cytotoxicity assay, but showed inhibitory action of tumor proliferation in vitro at an effector cell to target cell ratio of 500:1 in a [3H]thymidine incorporation assay. To determine if cytotoxicity could be induced against MOPC 104E-KI81 cells, in vitro sensitizing cultures were studied. We have demonstrated that normal BALB/c spleen cells became cytotoxic against MOPC 104E-KI81 cells after 5 days cultivation with mitomycin C-treated stimulator cells at an optimal responder to stimulator cell ratio of 5:1. Treatment of anti-Thy-1.2 serum plus complement abolished cytotoxic activity of effector cells. Cytotoxic cells lysed not only MOPC 104E-KI81 cells used for stimulation but also H-2k osteosarcoma cells. It was concluded that Thy-1.2-positive cytotoxic cells with nonspecific anomalous reactivity could be induced in murine plasmacytoma-stimulating cultures. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.