The short-term effect of a domestically produced equine antithymocyte globulin (ATG) was analyzed in 6 patients with acquired severe aplastic anemia (AA). All patients received 5 doses of ATG every other day in a 60-min intravenous infusion. Five peripheral blood immunoregulatory mononuclear cell (MNC) subsets, defined by monoclonal antibodies, were enumerated before and 24 h after each application of ATG. Following the first dose of ATG there was a significant and transient reduction in the absolute number of helper T lymphocytes. There was no statistically significant difference pre-ATG to post-ATG in the absolute number of MNC expressing activation antigen Tac (interleukin-2 receptor). However, Tac+ cells, which were significantly increased before ATG therapy, decreased to nearly normal levels after the fourth dose of ATG. A significant and sustained increment in the absolute number of monocytes (CD14+ cells) occurred following the third dose of ATG. The absolute numbers of MNC, suppressor T lymphocytes and cells bearing HLA-DR antigen remain without significant change along ATG treatment. These results suggest that: (a) Tac+ cells are probably involved in the pathogenesis of AA; (b) the target of ATG may be a Ta+ cell, and (c) ATG may stimulate monopoiesis.