Penetrance of H-2 histocompatibility antigens on the sialomucin-covered surfaces of TA3 mouse carcinoma cells growing in mice or rats was examined before and after sialidase digestion. Peripheral sialomucin did not appear to “mask” the antigenic phenotype of the cell membrane. The virulent hyperdiploid TA3 ascites tumor, derived from a spontaneous mammary adenocarcinoma in a female A/HeHa mouse, deviated from the usual strain specificity of near-diploid neoplasms. It outgrew immune reactions, killing all mice of 5 foreign strains as well as unconditioned adult rats of 4 strains. During syngeneic or allogeneic mouse passage, the tumor maintained exceptional karyotypic stability with a >90% mode of 41 acrocentric chromosomes, differing from the normal diploid mouse set by 1 additional small autosome. The rat-adapted TA3 cells also had this murine karyotype except for a large submetacentric marker chromosome. During prolonged heterologous immunoselection, it lost several H-2a antigens which are expressed on TA3 cells from syngeneic A/Ha mice. These isoantigens were irreversibly deleted, since they remained undetectable by hemagglutinin absorption, even after 6 months' passage of the rat-TA3 cells in A/Ha mice and after incubation with neuraminidase. However, neuraminidase consistently reduced electrophoretic mobility of the tumor cells by 53–65%, regardless of virulence or immunologic differences between the TA3 ascites and various experimental hosts. Degree of malignancy (as judged by host survival time) and antigenic disparity appeared unrelated to the net negative surface charge on these tumor cells.