Adriamycin (ADM) was found to have a two-step mode of action on the cardiac mitochondrial membrane. (1) An interaction with cardiolipin (CL) resulted in the formation of an ADM-CL complex able to transfer electrons from NADH to cytochrome c (cyt.c) as well as coenzyme Q (CoQ). This complex formation stimulates an increased activity of NADH-CoQ oxidoreductase (complex I) and CoQ-cyt.c oxidoreductase (complex III). (2) Transfer of electrons through ADM resulted in the formation of a very strong complex between ADM and CL. This new complex is different and much stronger than the already known ADM-CL complex.