Six hybrid cell clones were obtained by the fusion of Meth-A sarcoma cells (BALB/c mouse origin) and L(AG) cells (C3H mouse fibroblast) with the use of PEG 4000. The clones, named L-Me-A, B, C, D, E and F, were tested for their anti-tumor effects in mice. Each hybrid cell clone expressed both Meth-A sarcoma cell antigen and L(AG) cell antigen. Though each hybrid cell clone showed 51-88% of Meth-A sarcoma cell antigen, none of the clones produced tumors in normal BALB/c mice after s.c. inoculation of 10(6) cells. Normal BALB/c mice pretreated weekly with viable 10(6) L-Me-C cells for three weeks showed specific resistance to a challenge of Meth-A sarcoma cells. In the Winn assay, anti-tumor activity was observed in immune spleen cells and was lost by treatment with anti-Thy-1.2 antibody or anti-Lyt-1.2 antibody and complement, but not by treatment with anti-Lyt-2.2 antibody and complement. Adoptive transfer of this immune spleen cell fraction (Thy-1(+), Lyt-1(+)2(-) cells) to Meth-A sarcoma bearing mice was effective against tumor growth, too. Furthermore, inoculations of L-Me-C cells in BALB/c mice bearing Meth-A sarcomas depressed tumor growth remarkably. These results indicate that the anti-tumor immunity induced by hybrid cells was produced by Thy-1(+), Lyt-1(+)2(-) cells. It may be possible to apply this anti-tumor immunity not only to the prophylactic protection of normal hosts against the challenge of parental tumor but also to the therapy of hosts bearing parental tumors.