Staurosporine (ST), a potent inhibitor of protein kinase C (PKC), was evaluated for its effect on the proliferation of HT-29 colon adenocarcinoma cells; PKC is associated with increased colon cell proliferation. ST inhibited cell proliferation in a time- and concentration-dependent manner by up to 90%. It also blocked the G(2)/M phase of the cell cycle and induced classical apoptosis (sub-diploid peak on Bow cytometry, DNA ladder, and typical morphological changes). The kinetics of these changes suggest that low ST concentrations (2-20 nM) may act via a different mechanism from higher (100-1000 nM) ones. The role of ST, which is currently evaluated as an antitumor agent, in colon cancer requires further evaluation.