To study intra-arterial infusion of chemotherapeutic agents, human squamous carcinoma cells were obtained from the FaDu cell line and were implanted in athymic rats (rnu/rnu). The xenografts were grown and then were reimplanted on a vascular pedicle and were completely isolated from the surrounding tissue. The vascular isolation of these pedicles was confirmed radiographically and histologically. After 26 days of growth, an osmotic pump was implanted to deliver either saline, intra-arterial cisplatin, or intravenous cisplatin to the vascular pedicle. Platinum levels were identified in the tumors following intra-arterial and intravenous infusions, demonstrating the usefulness of this model for delivery of antineoplastic agents. We were unable to detect differences between tumor groups for final tumor volume, tumor platinum levels, and tumor histology with the one-dose schedule used. We were able to show a remarkable uniformity of the tumor platinum levels with varying serum platinum levels with intra-arterial and intravenous infusion of cisplatin. The toxicity of each drug administration method was assessed by levels of renal platinum and rat serum creatinine and blood urea nitrogen. No differences in toxicity with the dose administrated. We believe the immunodeficient rat with a xenografted isolated vascular pedicle is an excellent model to study the effect of intra-arterial therapeutic modalities on head and neck squamous cell carcinoma.