Recent studies using murine models of human squamous cell carcinoma (SCCA) have revealed a significant improvement in survival and cure rate of animals transplanted with human SCCA when treated with a combination of intratumor injections of chemotherapy and laser induced thermal therapy (LITT). These preliminary results suggest that this novel combination therapy may lead to improved clinical response compared to either treatment modality alone. Using a murine model of human SCCA we investigated two different modes of intratumor injection of cisplatin: a sustained-release cisplatin gel implant (CDDP/gel) versus cisplatin in solution (CDDP) at varying doses (range 1-3 mg/ml). In addition, we tested CDDP/gel combined with LITT. Results showed optimal drug concentration (30-300 nM) at tumor margins up to 4 h after injection of CDDP/gel implant compared to 3 nM at 5 min after injection with CDDP solution. Combined CDDP/gel and laser therapy significantly decreased tumor volume (P<0.05), with recurrence in only 25% of animals tested, compared to 78% tumor regrowth after LITT alone. These results suggest that laser chemotherapy may be an effective treatment for head and neck SCCA.