The immunodepressive and bone marrow stem cell-reducing activities of imidazole-4-carboxamide,5-(3,3-dimethyl-1-triazeno) (DTIC), an antitumoral agent reported to possess little immunodepressive capacity in man, have been investigated in mice and compared with those displayed by cyclophosphamide (Cy). In this species, single doses of DTIC could profoundly depress antilymphoma allograft resistance as well as the number of antibody-producing cells after primary and secondary stimulation with sheep erythrocytes. The highest immunodepressive activity was observed when DTIC was given before antigen and the effect observed was substantially more long lasting than seen with Cy, which was, however significantly more active on a milligram per kilogram basis. In contrast, both agents displayed a quantitatively equal activity in reducing bone marrow stem cells. It is concluded that DTIC can be an effective immunodepressant and that this activity may have clinical implications.