The virus-induced BALB/c lymphoma YC8 is known to be lysed in vitro by syngeneic lymphoid cells immune to non-H-2 antigens of B10.D2 and DBA/2 backgrounds. This tumor is weakly immunogenic in vivo and kills 100% of syngeneic mice with 1 X 10(3) cells given either intravenously (i.v.) or intraperitoneally (i.p.). We show here that i.v.-injected YC8 cells grow preferentially in the liver, where colonies become microscopically visible after 7-10 days, and, less frequently, in the kidneys and spleen but not in the lung. Passive adoptive immunotherapy of this tumor was carried out with alloimmune BALB/c anti-B10.A, anti-pool (donors were immunized with lymphocytes from 5 different strains), anti-A and anti-DBA/2 splenic and lymph node cells. When administered i.p. 1, 3 or 5 days after tumor cells had been given i.p. and with a schedule of 5 subsequent daily inocula, anti-DBA/2 lymphocytes cured 100%, 80% and 60% of animals respectively. A weaker effect was obtained with anti-pool immune cells whereas anti-B10.A and anti-A lymphoid cells had not therapeutic effects. When given i.v., the anti-DBA/2 immune lymphocytes were able to cure both i.v. and i.p. tumor-injected mice. A significant effect was observed also when the onset of immunotherapy was delayed until 7 or 10 days after tumor injection. By depleting the BALB/c anti-DBA/2 immune cells with appropriate monoclonal antibodies and complement, it was found that Lyt 1+ 2-cells played the major role in eradicating the neoplasm. in vitro phenotypic and functional analysis showed that the immune cell population included 70% of Thy 1+, 38% of Lyt 1+ and 18-20% of Lyt 2+ cells. Immune lymphocytes were not cytotoxic in vitro to YC8 or DBA/2 targets whereas they proliferated after restimulation with DBA/2 but only weakly with YC8 cells. This shows that it is possible to cure mice bearing a disseminated lymphoma which expresses non-immunogenic antigens recognized by BALB/c anti-DBA/2 immune T lymphocytes. These immune lymphocytes had no cytotoxic activity in vitro and their major effector cell subpopulation displayed the Thy 1+, Lyt 1+ phenotype.