The toxicity and antitumor efficacy of simian IL-15 was compared with human IL-2 in the context of syngeneic BMT. Groups of mice receiving or not receiving anti-CD3 activated splenocytes, termed "T-activated killer" (T-AK) cells, were treated between days 7 and 12 with escalating doses of IL-2 or IL-15 given twice daily. Recipients of IL-2+T-AK or IL-15+T-AK had significantly higher survival rates than saline+T-AK. Tissues from IL-2+T-AK, but not IL-15+Y-AK, treated mice revealed the presence of perivascular infiltrates in the lung and liver consisting of CD8+ T cells and Mac-1+ cells. Our findings demonstrate that IL-15 can be used effectively to stimulate antitumor responses post-BMT and may be associated with less toxicity than IL-2.