The anti-mitotic vinca alkaloids, vinblastine, vincristine, vindesine and navelbine, are widely used both as single agents and in combination with other antitumour drugs in cancer chemotherapy. Data on clinical pharmacokinetics following intravenous bolus injection, continuous infusion and oral administration show that vinca alkaloids are characterized by a large apparent total distribution volume, rapid total plasma clearance and a long terminal half-life. Faecal excretion is the main elimination route of vinca alkaloids in humans. Urinary excretion of these agents is generally low. Moreover, vinca alkaloid pharmacokinetics are time- and dose-dependent and show large inter- and intraindividual variability. When studied in various in vitro hepatic models (freshly isolated human and animal hepatocytes in suspension and in primary culture, isolated liver perfusion and human hepatic microsomal fractions), the vinca alkaloids were extensively biotransformed into a number of metabolites which have not yet been identified structurally. Incubation of vindesine and vinblastine with a library of human liver microsomal fractions demonstrated the involvement of the human hepatic cytochromes P4503A in the biotransformation of these and probably other vinca alkaloids. This finding is of great importance with regard to possible drug interactions between vinca alkaloids and other drugs administered concurrently in combination cancer chemotherapy.