Thirteen patients with pretreated, advanced inoperable squamous cell carcinoma of the head and neck were treated with a combination of oral 13-cis retinoic acid (1 mg/kg per day) and subcutaneous recombinant human interferon alpha-2a (3 million units per day). This regimen was administered for a period of six months on an outpatient basis, only interrupted when life threatening complications occured. On two patients the treatment was interrupted because of severe bleeding from the tumor site after one and four weeks of treatment. Four out of eleven patients (36 %) responded. One had a partial remission for 15 months. Another had a minor remission of two months duration. There were two patients with stable disease for three and five months. Dose reduction was necessary in one patient with severe anorexia and vomiting after six months of treatment and in two patients with hypertriglyceridemia grade 3. Most commonly seen toxic effects were mild fatigue, dryness of the skin, hypertriglyceridemia, and leukopenia grade 1-2. The combined systemic therapy with 13-cis retinoid acid and interferon alpha-2a is of certain effectiveness in the palliative treatment of squamous cell carcinomas of the head and neck especially in cases of high differentiation.