In the present study, we investigated the clinical and histopathological effects of CP therapy consisting of cisplatin (CDDP 50 mg/m2) or carboplatin (CBDCA 300 mg/m2) and peplomycin (PEP 5 mg/day) for 25 patients with oral squamous cell carcinoma. The effects of treatment and associated complications were as follows: 1) Complete response (CR) was achieved in 8 and partial response (PR) in 14 of the 25 cases. The overall clinical response rate was 88%. The histological response rate was 64%. 2) The clinical effects were not always consistent with the histopathological effects. There were discrepancies between the clinical and histopathological effects, especially in PR determined by clinical findings. 3) The principal adverse reaction was gastro-intestinal disturbances, but symptoms were able to be controlled. Signs of hematologic toxicity and renal disturbance were mild and did not preclude the continuance of therapy. The results of this study indicated that neo-adjuvant chemotherapy with CDDP and PEP was highly effective for the local control of oral squamous cell carcinoma.