Head and neck squamous cell carcinomas (HNSCC) frequently display increased levels of epidermal growth factor receptor (EGFR) and since the receptor is located on the cell surface, anti-EGFR antibodies appear to be suitable agents for antitumor therapy. We investigated the effect of murine EMD 55900 and rat ICR 62 monoclonal antibodies (MAb) directed against EGFR both as single agents and in combination with cisplatin. ELISA detection showed the amount of EGFR protein in HNSCC lines UM-SCC-10A, -10B, -11B, -14A, -14B, 14C, -22B and HLac 79, 8029NA, 8029DDP to range between 20 and 8100 fmol/mg protein. Compared to A431 cells, seven HNSCC lines were high and three low receptor expressors. Only low levels of TGF alpha were found in the supernatants of some untreated HNSCC lines, probably due to the consumption of TGF alpha by EGFR. Consequently, occupation of EGFR by MAb led to marked accumulation of TGF alpha in cell supernatants. Colorimetric MTT assay showed both MAbs (0.3-30nM) to have comparable dose-dependent growth inhibition which correlated with the EGFR content of the respective cell lines (p < 0.05). Using 30nM MAb, seven high receptor expressing HNSCC lines were growth inhibited by at least 20% to a maximum of 61% (mean = 38%). Combined treatment with MAb and cisplatin led to a significant decrease in cisplatin IC50 values in 5 cell lines expressing more than 1200 fmol EGFR/mg (dose modification by factor 2.1-4.1). In conclusion, anti-EGFR MAb exert direct antiproliferative activity in HNSCC lines and show additive effects in combination with cisplatin.