Paclitaxel, an antitumor drug that is demonstrating encouraging activity in human malignancies, is likely to play a major role in cancer chemotherapy. Paclitaxel has an unusual chemical structure--it is a complex diterpene having a taxane ring with a four-membered oxetane ring and an ester side chain at position C-13--and a unique mechanism of action. In vitro, paclitaxel enhances the polymerization of tubulin to stable microtubules and also interacts directly with microtubules, stabilizing them against depolymerization by cold and calcium, which readily depolymerize normal microtubules. The fact that the drug has a specific binding site on the microtubule polymer makes it unique among chemotherapeutic agents, and the ability of paclitaxel to polymerize tubulin in the absence of cofactors like guanosine triphosphate and microtubule-associated proteins is unusual. When paclitaxel and microtubule protein are irradiated with ultraviolet light, the drug preferentially binds covalently to the beta-subunit of tubulin. Paclitaxel binds to cells in a specific and saturable manner with a single set of high-affinity binding sites. The microtubule cytoskeleton is reorganized in the presence of paclitaxel and extensive parallel arrays or stable bundles of microtubules are formed in cells growing in tissue culture. Paclitaxel blocks cells in the G2/M phase of the cell cycle and such cells are unable to form a normal mitotic apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)