Leukemic cows and adult cattle in several herds under long-term surveillance were examined for the presence of antibodies to bovine C-type viruses (BLV) in order to investigate further the possible relationships between infection with this virus, bovine leukemia, and persistent lymphocytosis (PL). This latter condition is considered a preclinical stage of cattle leukemia by some investigators. Fluorescent antibodies reacting specifically with a virion antigen in the cytoplasm of BLV-infected cells were found in 90% of leukemic cows and in 80 to 100% of clinically normal cows with PL in multiple-case herds. The antibody titers of animals with PL were often lower than those of the leukemic cows. Clinically normal cattle with consistently normal lymphocyte counts in the multiple-case herds also showed fluorescent antibodies to BLV; however, in each of these herds the incidence (25 to 76%) and, in most cases, the titers of antibodies found in the nonlymphocytotic animal groups were lower than those of the corresponding PL groups. The antibody was also present in one-third of the cattle in a single-case herd in which the PL rate was not significant. In contrast, antibody was found in only 4 out of 214 animals from leukemia-free herds. In two multiple-case herds in which pedigree data are available, it was observed that animals from high-risk families had fluorescent antibodies to BLV at a significantly higher frequency, and often at higher titers, than animals from minimal-risk families. These data are consistent with the hypothesis that BLV may be the etiological agent of bovine leukemia and perhaps of PL but that host and virus factors may play significant roles in the host's response to BLV infection.

Virus was detected electron microscopically in 19 out of 20 antibody-positive cattle and in none of 12 antibody-negative animals examined. This shows that the fluorescent antibody test is as sensitive as electron microscopy for the demonstration of current BLV infection.

The distribution of precipitating antibodies reacting in immunodiffusion tests with the intraspecies group-specific (gs-1) BLV antigen among our various cattle populations correlated closely with the distribution of the fluorescent antibodies. This and the observation that semipurified BLV gs-1 antigen completely removes the specific fluorescent activity of our standard BLV reference serum indicates that the fluorescent and precipitating antibodies react with the same antigen. A comparison of the fluorescent and precipitating activities in the same bovine sera showed that the fluorescent antibody test is substantially more sensitive than the immunodiffusion test for the demonstration of BLV infection.

The significance of these data is discussed in terms of the value of the bovine system as a model for studies on the natural history of leukemia.