In vitro cross-resistance of adriamycin-resistant subline of P388 leukemia to non-anthracycline agents-actinomycin D, vincristine and vinblastine was elucidated. Decreased uptake of these 3 drugs was observed with the resistant cells. In addition, 2,4-dinitrophenol, a metabolic inhibitor, greatly enhanced the uptake of these drugs by the sensitive and resistant cell lines, particularly by the latter, abolishing a difference in drug uptake between the 2 which was observed under the normal condition. These results suggest that adriamycin-resistant cells are endowed with an enhanced capacity for outward transport of not only anthracycline antibiotics, but chemically and pharmacologically dissimilar agents such as the aforementioned agents.