In order to determine which cell supports BLV replication in experimentally infected sheep, peripheral blood lymphocytes (PBL) were separated into purified B and T populations by a panning technique. Our data demonstrate that viral replication takes place only in B lymphocytes. However, PHA, a T cell mitogen, is necessary for BLV replication both in PBL and enriched surface immunoglobulin bearing cells, whereas B cell mitogens have no effect on viral replication. Altogether, these results suggest that BLV activation in enriched B lymphocytes is dependent on the presence of residual T cells, and occurs through a T cell interaction, probably mediated by a soluble factor. This possibility was confirmed by the fact that the conditioned medium from cultures of BLV-free sheep T lymphocytes greatly enhances viral production by infected B lymphocytes. Our data favor the hypothesis that BLV multiplication occurs through the regular activation mechanisms of the immune system.