Immunohistochemical characterization of three monoclonal antibodies (MAbs), designated 323/A3, SF-25 and K928, on a panel of 330 head and neck and lung tumours indicated their potential for targetting tumours in the upper aerodigestive and respiratory tract. Subsequently, MAbs were screened in a clinical phase I/II radioimmunoscintigraphic (RIS) trial for the detection of primary tumours and lymphnode metastases in patients with histologically proven squamous cell carcinoma of the head and neck (HNSCC). In 10 HNSCC patients MAbs 323/A3 F(ab')2 (n = 3), chimeric (mouse-human) SF-25 IgG (n = 1), and K928 IgG (n = 6) were evaluated for their suitability for tumour targetting. Monoclonal antibodies 323/A3 and K928 were shown to be capable of detection of HNSCC. However, there was uptake at non-tumour sites, for MAb 323/A3 in the thyroid gland, liver and skeleton, probably bone marrow, and for MAb K928 in liver, spleen and the skeleton, probably bone marrow. At a higher K928 dose, uptake in the liver was diminished but still substantial. cSF-25 was not capable of detecting HNSCC, due to the rapid and extensive uptake at non-tumour sites such as liver, spleen, brain and the skeleton, probably bone marrow. Radioactivity uptake at non-tumour sites could be mainly explained by the presence of good accessible antigenic sites and will definitely limit the application of these pan-carcinoma MAbs for therapeutic purposes.