A murine lymphosarcoma (LS-1) which originated spontaneously in a DBA/2 mouse, was evaluated as a model of malignant lymphoma for drug screening and combination chemotherapy. Antitumor activity was distinct in the order of L-asparaginase (LASP), mitoxantrone, a new anthraquinone analogue (MIT), ifosfamide (IFO), cyclophosphamide (CPA), adriamycin (ADM), and aclarubicin, a new ADM analogue (ACR), when measured as increased life span of mice intravenously implanted with LS-1 and intraperitoneously treated with antitumor agents at an optimal dose. Methotrexate (MTX), vincristine (VCR), and vindesine (VDS) were marginally active against LS-1. Nitrosourea compounds, such as BCNU and ACNU, and bleomycin were inactive against the tumor. The murine lymphosarcoma, LS-1, appeared to provide a drug activity spectrum closely analogous to malignant lymphoma in man except for LASP. The combination of IFO and MIT was the most effective among six 2-drug combinations. CPA and MIT, IFO and ADM, and CPA and ADM were also effective combination. ACR, however, appeared antagonistic to IFO and CPA, since in combination with these agents, ACR did not prolong the life-span at any dose, as compared to the optimal dose of IFO or CPA alone. The murine experimental system using LS-1 should be usefull as a chemotherapy model of malignant lymphoma in man.