The objective of this proposal is to develop new and effective therapeutic approaches involving immunotherapy for the treatment of non-resectable malignant disease based on studies in dogs with spontaneous neoplasms. The specific aims of the research to be conducted are as follows: 1. To detect tumor-associated antigens (TAA) and survey reactivity against such antigens both before and during therapy using several in vitro assays, including lymphocyte blastogenesis, cytotoxicity assessed by 51Cr release, and migration inhibitory factor production. 2. To perform allogeneic mmrrow grafts following total body irradiation (TBI) in order to assess the "adoptive" immunotherapeutic effect of allogeneic marrow. 3. To assess the antitumor effect of various immunotherapeutic maneuvers, e.g. infusion of sensitized lymphocytes, administration of killed tumor cells or use of in vitro sensitized marrow or lymphocytes, in conjunction with TBI. Both clinical response and change in in vitro reactivity against TAA will be measured. 4. To assess the antitumor effect of high dose dimethylmyleran (DMM) in conjunction with autologous marrow rescue in dogs with malignant tumors. The absence of immunosuppression following high dose DMM makes its use in conjunction with immunotherapy particularly attractive. 5. To assess the effect of malignant neoplasms on turnover of hemostatic factors, i.e., platelets and fibrinogen.