Over the past year, we have discovered a new aspect of adriamycin chemistry which may have profound implications for its action in vivo. Briefly, adriamycin binds tightly to iron to yield on adriamycin iron chelate. This chelate in turn is able to catalyze the transfer of electrons from reduced thiols such as glutathione to molecular oxygen. The products produced include superoxide, hydrogen peroxide and hydroxyl radical. Because the adriamycin iron chelate also binds to cell membranes and to DNA, it is able to cause damage to these macromolecules. Our plans over the next year include: 1) achieve an understanding as to the mechanism of the catalysis produced; 2) do structure activity studies in order to determine what other drugs may possess this mechanism of action; 3) determine what role this complex plays in vivo.