The relationship was analyzed between cell kinetics, defined as3H‐thymidine labeling index (3H‐TdR LI), and clinical responses for 35 previously untreated patients with locally advanced oral cavity squamous cell carcinomas. Patients were treated with three cycles of vincristine and bleomycin (VB) or of VB plus methotrexate (VBM), given by intra‐arterial infusion followed by surgery. The objective clinical response rate was higher after VBM treatment than after VB, whereas overall clinical response rates were similar for patients with slowly or rapidly proliferating tumors. The probability of relapse‐free survival at 4 yr and overall survival was significantly higher for patients with high3H‐TdR LI tumors given VBM than for those given VB. For patients with slowly proliferating tumors, there were no differences in relapse‐free survival and overall survival between the two treatments. These data suggest that patients with rapidly proliferating tumors benefit from primary intensive chemotherapy treatment including methotrexate and that cell kinetics can be used to formulate rational clinical protocols for oral cav