The studies described in this report demonstrate that 1-adamantanamine hydrochloride (amantadine) is a potent enhancer of the cytotoxic activity of the anti-pan-T lymphocyte (CD5) T101 monoclonal antibody conjugated to purified ricin A-chain (T101-immunotoxin; T101-IT). We also demonstrate that T101-IT in the presence of amantadine does not induce immunotoxin-mediated cytotoxicity in nontarget cells such as human marrow hematopoietic progenitor cells. These results provide further knowledge for the improvement of ex vivo purification of human bone marrow from normal or leukemic T cells prior to allogeneic or autologous stem cell transplantation, respectively. Furthermore, since amantadine has long been employed safely in human therapy, its use in conjunction with immunotoxins might be exploited in vivo