Summary Canine transmissible venereal sarcoma (CTVS) is a naturally occurring contagious neoplasm which can be transplanted with intact viable cells across major histocompatibility (MHC) barriers within the species and even to other members of the canine family, such as foxes, coyotes, and wolves. After 2 to 4 months of progressive growth the tumour regresses spontaneously in adults but metastasizes in immunosuppressed hosts and neonates. The mechanisms of how the tumour cells manage to overcome histocompatibility barriers so successfully for such a long period and yet succumb later are not known. In the present study we found that CTVS cells were not stimulatory to the lymphocytes of normal or tumourbearing animals in mixed lymphocyte-tumour reaction (MLTR), although the lymphocytes from tumourbearing hosts responded well to either phytohaemagglutinin (PHA) or third-party allogeneic lymphocytes. Immunofluorescent antibody (IFA) assay of MHC antigens by monoclonal antibodies (MoAb) to monomorphic Class I and Class II MHC antigens showed that progressor tumour cells lacked the expression of the antigens whereas 30 to 40% of regressor tumour cells expressed them.