A short-term antimetabolic assay based on the interference with 3H-thymidine and 3H-uridine incorporation after 3 hours of in vitro treatment was used to compare the cytotoxicity of a new halogenated anthracycline, 4'-Iodo-4'-deoxydoxorubicin (IDX), with that of its parent compound Doxorubicin (DX) against 44 human colorectal carcinomas. IDX had a marked dose-dependent effect, with frequencies of activity consistently greater than those of DX at all concentrations. The minimal dose of IDX required to induce a significant antimetabolic effect obtained by extrapolation from the dose-effect plots for each drug was 1/10 that of DX (2.3 micrograms/ml vs 23 micrograms/ml). When the relative activities of the two drugs on the same tumor specimen were determined, there was 71% to 86% overall agreement, depending on the concentration used. Lack of agreement was always attributed to sensitivity to IDX and resistance to the parent compound.