Resting peripheral blood mononuclear cells (PBMC) or purified T-cells can be induced to proliferate when cocultured in vitro with fixed HTLV-infected T-cells. This process of HTLV-dependent cellular activation and induction of proliferation has been considered distinctive because of an apparent independence from conventional T-cell costimulatory signals. We have examined several HTLV-infected cell lines and found that proliferation was readily induced in resting PBMC by T-cells that were productively-infected with HTLV. However, equivalent HTLV-productive infection in a B-cell line failed to induce proliferation in PBMC, suggesting that HTLV-dependent induction of proliferation in PBMC was, at least in part, dependent upon a T-cell-specific signal. Furthermore, the induction of proliferation in PBMC populations was found to overlap with, and actually require, transfer and establishment of HTLV infection within the T-cell compartment of the PBMC population. These findings suggest that virus-induced activation of target cells may be directly associated with transfer and spread of HTLV infection. (C) 1996 Academic Press, Inc.