Proapoptotic synergy between the antiestrogen, 4-hydroxytamoxifen (4-OHT) and the plant toxin, persin is mediated via an upregulation of Bim mRNA in human breast cancer cells. A combination of nontoxic concentrations of persin (2.76 μmol/L) or 4-OHT (7.5 μmol/L) leads to a significant enhancement of apoptosis compared to single agent treatment, and this is associated with the increase in Bim mRNA shown. Knock-down of Bim expression with specific siRNA abrogates this synergistic response. For details, see Roberts et al. in this issue.