Splenocytes immune to a highly immunogenic ("xenogenized", L5178Y/DTIC) variant of a murine lymphoma exert anti-parental-tumor activity in a systemic adoptive transfer system, the effect being apparently associated with the Lyt-2- fraction of the lymphocyte population. During investigation of the mechanisms of this protection, we found that the L5178Y/DTIC tumor-immune lymphocytes exhibited an appreciable anti-L5178Y delayed-type hypersensitivity (DTH) response. Enrichment of those lymphocytes in L3T4+ cells significantly enhanced the protective effect as well as the DTH reaction, whereas the use of an anti-L3T4 but not anti-Lyt-2 reagent blocked both activities. In vitro, lymphocyte proliferation against L5178Y cells occurred and was apparently associated with the Lyt-2- fraction of a population of L5178Y/DTIC immune splenocytes.