A study of MCF-7 human breast cancer cells was undertaken to ascertain the degree of apoptosis induction by paclitaxel and if the induction of apoptosis could be enhanced by caffeine. Paclitaxel (0-20 ng/ml) caused concentration-dependent increases in morphologically identifiable apoptotic cells (up to 43% of cell population) and cells with DNA strand breaks (up to 38%), a commonly cited marker of apoptosis. Maximal DNA strand breakage occurred after 16 hr of exposure to paclitaxel and maximal apoptotic-appearing cells occurred after 24 hr. The remaining non-apoptotic paclitaxel-exposed cells were growth arrested in G2. A 4-hr exposure to caffeine concentration-dependently (0-20 mM) increased apoptosis to 88% of the cell population. Our results show induction of apoptosis in breast cancer cells by paclitaxel, and enhancement of this process by caffeine.