Amphotericin B was able to enhance the effects of actinomycin D (Act-D), adriamycin, and vincristine against AKR leukemia. AKR leukemia lines of increasing resistance to Act-D were obtained by passage in syngeneic mice treated with Act-D. The cells selected for Act-D resistance also eventually became cross-resistant to vincristine and Adriamycin, but resistance to these agents developed at a slower rate. Amphotericin B enhanced the effects of all these agents against the resistant cells, although the degree of enhancement varied among these antitumor agents and decreased as drug resistance increased in the late-passage leukemia lines.