Qualitative and quantitative aspects of the interaction between anthramycin methyl ether (AME) and DNA have been investigated spectrophotometrically by utilizing alterations in the anthramycin methyl ether spectrum that result from complex formation. Certain nucleic acid polymers, purine and pyrimidine derivatives, and various agents have been employed in examining the molecular nature of the interaction. These experiments suggest that binding involves both electrostatic attraction between the AME and the anionic phosphate groups of DNA, and a more specific interaction apparently involving seven-membered ring portions of AME and DNA. The secondary structure of DNA also affects its binding to AME. The ability of the compounds of the anthramycin series to complex with DNA was correlated with their biological activity. The possibility of predicting biological activity of a new compound from this series by using only spectrophotometric assay is therefore indicated. © 1968.