This report describes a new animal model for active, specific, systemic immunotherapy of leukemia. Mice were challenged (day 0) with 10(3) viable LSTRA cells and treated later with a vaccine containing 10(7) irradiated LSTRA cells. Four intraperitoneal or intravenous vaccine injections, on days 2, 9, 16 and 23, caused significant prolongation of survival; single injections by the same routes had inconsistent effects. Vaccine was not effective against a higher initial challenge dose, when given later in the course of tumor growth, when given intradermally or when used in weanling mice. The therapeutic effect was specific since a vaccine composed of an antigenically unrelated leukemia was ineffective. These results suggest that LSTRA is suitable for studying active, systemic, specific immunotherapy.