A human tumor cloning system was used to assess the cytotoxicity of adriamycin, mitoxantrone and bisantrene at concentrations that are equitoxic in man. There were 989 specimens evaluable for drug sensitivity analysis. Overall, adriamycin showed in vitro cytotoxicity (greater than or equal to 50% decrease in tumor colony forming units) 14% of the time; mitoxantrone, 21% of the time; and bisantrene, 31% of the time. Three hundred ninety-nine of these evaluable specimens were simultaneously tested against more than one of the agents, providing 631 two-way drug comparisons. For these comparisons, there was lack of co-resistance 27-34% of the time, with mitoxantrone being more active than adriamycin (p less than .05) and bisantrene being more active than adriamycin (p less than .01) or mitoxantrone (p less than .01). These data suggest that comparative and sequential clinical use of these agents should be investigated.