Romidepsin, a selective inhibitor of histone deacetylases (HDACs), was approved for the treatment of cutaneous T-cell lymphoma in November 2009 by the U.S. FDA. Romidepsin is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. Romidepsin strongly down-regulated expression of the immunosuppressive cytokine, interleukin (IL)-10, frequently overexpressed in CTCL, at both the RNA and protein level in CTCL cell lines and at the RNA level in primary CTCL cells. Romidepsin also increased expression of IFNG RNA and decreased expression of IL-2 and IL-4 RNA, although to a lesser extent compared to IL-10. Romidepsin strongly inhibits HDAC1 and HDAC2 with IC50 of 1.6 nM and 3.9 nM, respectively, but is relatively weak in inhibiting HDAC4 and HDAC6 with IC50 25 nM and 790 nM, respectively. Romidepsin inhibits the growth of U-937, K562, and CCRF-CEM cells with IC50 of 5.92 nM, 8.36 nM, and 6.95 nM, respectively. Romidepsin