Lymphocyte proliferation responses were investigated in sheep and cattle, in which the replication of bovine leukemia virus (BLV) had been known to be suppressed by inoculation with recombinant vaccinia virus (rVV) expressing BLV envelope glycoprotein (gp60). Enhanced lymphocyte proliferation responses were observed in animals inoculated with rVV, regardless of whether they were naive or BLV carriers. These responses were roughly inversely correlated to the growth of BLV in the peripheral blood leukocytes. In contrast, there was no apparent correlation between humoral immune response and BLV growth. Based on these results, it was suggested that rVV rendered its suppressive effect of BLV replication primarily via augmentation of cell-mediated immunity.