The anthracycline anti-cancer drug adriamycin (Adr) was coupled to human transferrin (Trf) by using a glutaraldehyde technique. The effect of Trf-Adr conjugates and unconjugated Adr on human cells was determined by using normal peripheral blood mononuclear cells and chronic myelogenous K562 cells. Cytotoxicity was determined by using an assay that measures the conversion of a tetrazolium salt (MTT) into a purple product (formazan) by mitochondrial dehydrogenases in viable cells. We found that free Adr at a concentration of 1 x 10(-7) had little effect on K562 cells, while Trf-Adr conjugates inhibited 75% of cellular activity. When normal peripheral blood mononuclear cells were tested against Trf-Adr conjugates, the 50% inhibitory concentration was found to be 1.4-1.7 x 10(-6) M, at which concentration greater than 85% of K562 cells were inhibited. Interactions of Trf-Adr conjugates with plasma membrane energy-producing systems are the proposed mechanisms of cytotoxicity.