Human T-cell-leukemia-virus-type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The T-cell-targeting immunosuppressants, FK506 and cyclosporin A (CsA), suppressed proliferation of the HAM/TSP-derived T-cell lines, H89-59, H89-79 and H109. FK506 and CsA also reduced expression of the proto-oncogenes, c-myc and c-fos, but not c-jun and interleukin-2-receptor-alpha (IL-2R alpha) gene in H109 cells. The growth-inhibitory effects of FK506 and CsA were not abrogated by interleukin 2 (IL-2). These results suggest that the inhibitory effects of FK506 and CsA are independent of IL-2, and are associated with the reduction of c-myc and c-fos gene expression.