Cellular uptake and cytostatic activity of 4'-O-tetrahydropyranyladriamycin (THP) in various sublines resistant to anthracycline antibiotics of mouse lymphoblastoma L5178Y, Chinese hamster ovary (CHO) and mouse leukemia P388 cells were studied. All the sublines resistant to adriamycin (ADR) showed slightly decreased uptake of THP as compared with each sensitive lines, but THP was still taken up much more quickly than ADR by each of the ADR-resistant cell lines. Efflux of both anthracycline glycosides from the ADR-resistant P388 cells was faster than that from the ADR-sensitive P388 cells. The percentage of THP retained at equilibrium was higher than that of ADR in both ADR-resistant and -sensitive P388 cells. Cytotoxicity of THP to ADR-resistant cell lines was considerably lower compared with that for each of the sensitive lines but THP inhibited growth of ADR-resistant tumor cells at a concentration about 10 times lower than that for ADR. Thus THP was taken up more quickly, effluxed more slowly than ADR from the ADR-resistant cells, and showed stronger cytostatic activity than ADR on the cells.