5-Fluorouracil (5-FU) and 2 alpha-methyldihydrotestosterone propionate (MDTP) have effectively induced complete regressions of induced rat mammary carcinomas; in combination, regressions were additive and synergistic. Present aims were to determine whether similar antitumor effects were obtainable with a human mammary carcinoma, MCF-7, and to affirm the synergism of 5-FU and MDTP. After incubation in vitro for 3 days and exposure to drug for another 2 days, cell counts and/or determinations of total cell protein revealed growth inhibitions of 16-87% by 5-FU at 130-1300 micrograms/ml and 16-94% by MDTP at 0.36-360.5 micrograms/ml. Combinations of 5-FU and MDTP at the same inhibitory doses (ID) yielded approximately additive growth inhibitions. Algebraic and geometric (isobole) methods of analyses showed that these inhibitions were additive or synergistic, depending on the iso-effective dose used. Precursor incorporation into macromolecules also showed approximately additive effects for MCF-7 cells treated with 5-FU and MDTP, each at ID15. These data demonstrate significant additive growth-inhibitory activity of 5-FU and MDTP in combination against MCF-7 in vitro, thus affirming their antitumor effects in vivo.