Indicine N-oxide is the first member of the large class of compounds comprised of pyrrolizidine alkaloids and their N-oxides to be studied in the treatment of cancer in humans. Twenty-two patients with refractory acute leukemia received indicine N-oxide daily for 5 consecutive days in a dose-seeking study. Of eight patients with refractory acute lymphocytic leukemia, one had a complete remission, and one had a partial remission. Of 11 patients with refractory acute nonlymphocytic leukemia, 2 patients had complete remissions. Of three patients with blast crisis of chronic granulocytic leukemia, one patient had a partial remission. Five patients had severe hepatic toxicity, probably due to veno-occlusive disease induced by the drug. Whether hepatotoxicity and antileukemic activity are a result of the same mechanism of action of indicine N-oxide is not known.