Iodo-doxorubicin belongs to the group of doxorubicin analogs with modifications at the 4'-position of the daunosamine sugar moiety. Epirubicin is the archetype of the analogs created by configurational changes at the sugar. In case of EPI, the hydroxy group at the 4'-position is equatorial instead axial. In case of I-DOX, the hydroxy group has been replaced by an iodine-atom. This exchange has a great influence on the basicity of the amino group at the 3'-position. The physico-chemical properties of I-DOX are markedly different from those of DOX and EPI. I-DOX is unprotonated at physiological pH and much more lipophilic than DOX. The preclinical screening showed greater potency of I-DOX in different tumor cell systems. Cardiotoxicity and tissue toxicity after extravasation were significantly reduced in case of I-DOX. The substance was evaluated within three phase-I-studies in Europe during 1988 to 1990. The most prominent toxicity observed was myelotoxicity. This type of toxicity was dose-dependent and reversible. Alopecia, stomatitis/mucositis were not seen at all. There was only minor nausea without vomiting. The measured thyroid parameters were not affected by administration of an iodine-containing drug, but long-term effects cannot be ruled out. No acute cardiotoxicity was observed. The pharmacokinetics and metabolism of I-DOX differ from those of DOX and EPI. The terminal half-life of I-DOX is shorter, the plasma clearance higher than of DOX. One major difference is the formation of iodo-doxorubicinol, which is much larger in case of I-DOX compared to DOX and EPI. This cytostatic metabolite has a long terminal half-life.