It has been the aim of the present investigation to study the effect of intratumorally applied human fibroblast interferon (nIFN-beta; Fiblaferon 5 for the first two weeks, and Fiblaferon 3 three times a week) in a phase-II clinical trial of thirteen patients with advanced head and neck squamous cell carcinomas. All of the patients had failed established therapeutic modalities before and could not be treated by conventional procedures. nIFN-beta was injected intratumorally and its effect on tumour size was assessed by an independent, second observer as well as via CT and MR imaging. All assessments were done prior to treatment, 8 weeks after beginning treatment and at 16 weeks. Three female and ten male patients with primary tumours of the hypopharynx (n = 5), the larynx (n = 4), the oropharynx (n = 1), the glandula submandibularis (n = 1), the oral cavity (n = 1) and the oesophagus (n = 1) have undergone outpatient treatment three times a week. Tumour size showed no change in six patients while progressive disease occurred in seven cases after eight weeks of treatment. Radiological findings did not change in the nine patients continuing treatment while five showed progressive disease. There were no serious local or systemic side effects due to the intratumoral nIFN-beta treatment. The survival time was 9.73 months after the onset of nIFN-beta treatment.