ABSTRACT: We have used transferrin-adriamycin conjugates to deliver drug to transferrin receptors and have shown that the conjugates bind to and kill tumor cells in vivo and in vitro. This has been studied with the use of qualitative and quantitative assays. In this report, we present evidence indicating that the primary target of transferrin-adriamycin cytotoxicity is the plasma membrane. This was done using a spectrofluorometric method that takes advantage of the fluorescence properties of adriamycin. It was shown that, while DNA intercalation may be the primary mechanism of cytotoxicity for free adriamycin, transferrin-adriamycin conjugates were not observed to interact with nuclear DNA. This may be a useful consideration in the design of future chemotherapeutic studies with transferrin conjugates of anticancer drugs.