Objectives: The combination of Taxol with a platinum-based chemotherapy is now the standard first-line chemotherapy following surgical debulking in the treatment of ovarian cancer. Approximately 25% of patients fail this treatment and are deemed Taxol-platinum resistant. However, it is unclear if these patients are resistant to both drugs or to one drug that exhibits mechanistic dominance. We set out to determine how Cisplatin and Taxol interact in vitro and whether one has a dominant effect over the other.Methods: We analyzed eight human ovarian cancer cell lines, including Cisplatin-sensitive and -resistant lines. The cells were exposed to clinically relevant doses of Cisplatin (33 μM) and Taxol (2 μM) for 3 hours and allowed to incubate for 48 hours. We assessed responses to Taxol and Cisplatin alone or in combination by 4 separate methods. Cell killing was assessed by cytotoxicity assays. Apoptosis was evaluated using DNA laddering and immunofluorescent microscopy. Cell cycle effects were assessed using flow cytometry.Results: Combination treatment resulted in a decrease of Taxol-induced cytotoxicity by 0-18.4%. This loss was mirrored in apoptosis assays where Cisplatin reduced or blocked Taxol-induced DNA fragmentation. In all cell lines tested, the cell cycle profile of combination treated cells reflected that of Cisplatin alone, with cells accumulating in G 2 /M and an absence of hypodiploid cells.Conclusion: These results suggest that Cisplatin exerts preferential dominance over Taxol when used in combination therapy. As Cisplatin-resistant cells show sensitivity to Taxol, patients who fail to respond to combination Taxol-platinum therapy may significantly benefit from a trial of Taxol alone.