Background. Recently a combination therapy of squamous cell carcinomas (SCC) of the head and neck and the cervix with interferon-alpha 2a (IFN alpha-2a) and 13-cis retinoic acid (13-cRA) had been presented. Our aim was to check the effectiveness of this therapy as a palliative treatment on SCC of the oral cavity. Methods. A total of 13 patients with pretreated, advanced, inoperable SCC of the head and neck were treated with a combination of 13-cRA and IFN alpha-2a (3 million units per day). This regimen was administered on an outpatient basis, only interrupted when life threatening complications occurred. Results. The treatment had to be interrupted in two patients because of severe bleeding from the tumor site. Of II evaluable patients four responded, one had a partial remission for 15 months. Another one had a minor remission of 2 months. There were two patients with stable disease for 3 and 4 months. Most commonly seen toxic effects were mild fatigue, dryness of the skin, hypertriglyceridemia and low grade leukopenia. Conclusion. The combined systemic therapy with 13-cRA and IFN alpha-2a is of a certain, limited effectiveness in the treatment of SCC of the oral cavity especially in cases of high differentiation.