We have previously shown that YC8, a Moloney virus-induced BALB/c lymphoma, is susceptible to lysis by BALB/c anti-DBA/2 effector cells. To further evaluate the relationship between non-H-2 antigens of DBA/2 background and tumor-associated determinants, we investigated the pattern of cytotoxic and proliferative responses induced in BALB/c mice by immunization with YC8 lymphoma. Spleen cells from tumor-immunized animals were restimulated in vitro with YC8 cells and tested for cytotoxicity on target cells of different strains and haplotypes. Cytotoxicity was observed only against YC8, DBA/2 blasts, and P815 (a DBA/2 mastocytoma). BALB/c anti-YC8 effectors were equally blocked by unlabeled YC8 and P815 cells when assayed on YC8 labeled targets. A clonal analysis, however, revealed the existence of at least two types of effectors, one lyric for both P815 and YC8 cells, the other lyric for YC8 cells only. BALB/c anti-YC8 cells proliferate when stimulated both with YC8 and DBA/2 cells in the presence of accessory cells. When tested in an adoptive transfer assay, anti-YC8 cells given i.v. cured 100% of i.v. and 75% of i. p. tumor-injected mice, respectively. When given i. p. anti-YC8 effectors cured 100% of i. p. tumor-injected animals. These results confirm the expression of non-H-2, DBA/2-1ike antigens on the BALB/c lymphoma YC8 and reveal the presence of additional tumor-associated determinants; both sets of antigens may induce a cellular immune response and elicit immune lymphocytes which can eradicate YC8 cells in an adoptive immunotherapy assay.