In an effort to enhance the antigenicity of canine tumor cells, canine interferon-gamma (CnIFN-gamma) was applied in vitro to seven canine mammary tumor (CMT) and two canine melanoma (CML) cell lines. Surface expression of major histocompatibility complex (MHC) antigens and tumor associated antigens (TAA) was measured by a flow cytometric fluorescence assay using commercially available anti-MHC antibodies, and anti-canine TAA monoclonal antibodies generated against CMT and CML cell lines. Compared to constitutive antigen levels in untreated cells, treatment with CnIFN-gamma resulted in increased expression of MHC class I and II antigens (up To 19-and 167-fold, respectively) and a TAA (up to 5-fold) by CMT cell lines, and increased expression of class I antigen (131-fold) by one CML and of class II antigen (18-fold) by the other CML cell line. Expression of MHC antigens and a TAA by tumor cells was increased by Cn-IFN-gamma treatment, and such an increase may be of potential benefit in tumor cell recognition and rejection by the immune system.