The effectiveness of Doxil as a new chemotherapeutic agent against canine transmissible venereal tumor was evaluated, using NOD/ SCID and CD1-nu xenograft mouse models and the response between the two mouse strains was compared. Samples of xenografted venereal tumor were inoculated SC into 20 six week-old NOD/SCID mice and 20 six week-old CD1-nu mice. Seven weeks later, tumor-bearing mice were divided into treatment and control groups. Treatment group was injected with Doxil (6 mg/kg, IP, as a single injection). Control group was injected with buffered saline (0.75cc, IP). Tumor size was determined by caliper measurements and tumor response was assessed according to standard criteria. In both strains there was a significant decrease in tumor size in response to Doxil treatment (P<0.0001). In CD1-nu eight out of nine tumors (88%) responded to the treatment, and in 2 cases complete remission was observed. In NOD/SCID group response to the treatment was seen in eight out of ten tumors (80%) but none regressed fully. Response to the treatment was statistically equal in both strains even though the apoptotic rate, confirmed by TUNEL staining, was higher in NOD/SCID than in CD-1-nu (8.65% and 0.7%, respectively) and tumor infiltrating cells were different: eosinophils in NOD/SCID and CD45R-positive B lymphocytes, and plasma cells in CD-1-nu. In untreated CD1-nu mice, tumor progress was slower than in NOD/SCID. Our results indicate that Doxil is effective against CTVT in mouse xenograft models.