Sera of female and male mice from eleven inbred mouse strains collected at either 4, 12, 36 or 60 weeks of age were tested for the presence of natural antibodies to the murine mammary tumour virus by means of the Sepharose bead immunofluorescence assay. Antibodies to the virus proved to be ubiquitous, but pronounced strain differences were found in titer and onset of antibody production. These differences were related to neither release of virus in the milk nor susceptibility to spontaneous mammary tumour development of a given strain. Immunological specificity of the observed reactions was concluded from a) the failure to block the reaction by absorption with fetal calf serum, mouse milk or sheep erythrocytes, while absorption with purified virus abolished the reactivity; b) the lack of reactivity of rat sera with the mouse mammary tumour virus in this system; c) the negative response of mouse sera with Sepharose beads coated with ovalbumin; d) the lack of correlation between antibody titers to Rauscher murine leukemia virus and mammary tumour virus in this system; e) the retaining of activity to highly purified viral polypeptides; f) blocking of the reaction by preincubation with rabbit anti-mouse immunoglobulin serum or Protein A from Staphylococcus aureus. Since germfree mice of various strains also have such antibodies, it is concluded that the reactions are not due to horizontal transmission of the virus. From the lack of correlation between antibody titers and tumour incidences, it is concluded that various systems overshadow the potential immunosurveillance role of such natural antiviral antibodies.

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