In combined modality treatment, cisplatin and fluorouracil are considered to act synergistically. The assumption is based on results in murine leukemias and has not hitherto been tested on human squamous cell carcinoma. In the present study, cisplatin and fluorouracil, used singly and in combination, were tested on two human squamous cell carcinomas of the head and neck, xenografted to nude mice. Cisplatin (7.5 mg/kg) was given as a single-dose intraperitoneal injection and fluorouracil as repeated intraperitoneal injections every eight hours for four days to a total dose of 200 mg/kg. The toxicity of the cisplatin and fluorouracil combination was lower (27%) than that of fluorouracil alone (50%). Both drugs gave a dose-dependent inhibition of tumor volume growth. Using gained growth delay as endpoint, cisplatin and fluorouracil therapy exhibited a synergistic effect on both tumor lines.