We investigated the effect of toremifene, interferon-alpha2a, interferon-alpha2b and interferon-alpha2c, singly and in combination for their effect on the growth of ZR-75-1 human breast cancer cells. Median effect analysis was used to determine synergistic or additive effects. Anti-proliferative studies showed that the growth of ZR-75-1 cells was inhibited to a greater extent by combination treatment with toremifene plus interferon-alpha2a, resulting in a synergistic interaction (CI <1) for all concentrations tested. A combination of toremifene plus interferon-alpha2b resulted in a synergistic interaction (CI <1) for the two highest concentrations of toremifene (10(-6) and 10(-7) M) and an additive effect (CI approximately equal to 1) for the lower concentrations (10(-8) to 10(-10) M). When toremifene was combined with interferon-alpha2c no additive or synergistic interaction was determined.