Replacement of the 3'-methoxy group of the clinical antileukemic agent amsacrine with a 3'-methylamino group provides a compound (3) with a broader spectrum of action, including in vivo activity against experimental solid tumors. The synthesis, physicochemical properties, and biological activity of a series of acridine-substituted analogues of 3 are described. The compounds show higher levels of DNA binding, water solubility, and in vivo solid tumor activity (lewis lung carcinoma) than their amsacrine counterparts. However, the structure-activity relationships for acridine substitution are different, with 3,5-disubstituted 3'-methylamino compounds showing the highest activity (compared to 4,5-disubstituted amsacrine analogues).