The plasma level of 4'-O-tetrahydropyranyladriamycin (THP) declined rapidly after IV injection to mice, with a t1/2(alpha) of 0.453 min. Only 1.2 micrograms/ml THP was detected 2 min after injection of 5 mg/kg. The drug was immediately transferred to various tissues, where the drug levels were much higher than the plasma concentration. In the lung and spleen, 8.26 and 13.6 micrograms/g THP was present, respectively, 2 h after administration. Major metabolites of THP were 13-dihydro-THP, ADM, 7-deoxyadriamycinone, and 7-deoxy-13-dihydro-adriamycinone. Only 1.12% of the dose had been recovered in the urine by 48 h after injection as THP and its metabolites, according to analysis by HPLC fluorospectroscopy. The observed disposition of THP was compared with that of adriamycin (ADM). The plasma disappearance and tissue transfer of THP were faster than those of ADM. THP levels in the spleen and lung were higher and those in the heart and liver were lower than the corresponding ADM levels. Drug levels declined more quickly in most tissues in the case of THP than of ADM. Tissue distributions after single bolus and multiple injections were also compared and discussed.