Water-soluble extracts of edible Vernonia amygdalina leaves were recently reported as potent inhibitors of cultured MCF-7 cells. The mechanism by which V. amygdalina inhibits MCF-7 cell growth has not been previously studied. The objective of this study was to evaluate the effects of V. amygdalina on the activities, DNA synthesis, and subsequent cell growth of extracellular signal-regulated protein kinases 1 and 2 (ERKs 1/2;). Treatment of cells with various concentrations (3-100 mg/ml) of water-soluble V. amygdalina extract potently inhibited ERK activities, DNA synthesis (P < 0.005), and cell growth (P < 0.01) in a concentration-dependent fashion, both in the absence and presence of serum. The growth rate of cells pretreated with 10 mg/ml V. amygdalina for 48 hrs before transfer to V. amygdalina-free medium was not significantly different (P > 0.05) from untreated cells. These results suggest that V. amygdalina, at least at concentrations up to 10 mg/ml, exhibits cytostatic action to retard the growth of human breast cancer cells. In addition, the ERK signaling pathways may be one or more of the intracellular targets for V. amygdalina antineoplastic actions.