AbstractUnregulated expression of epidermal growth factor receptor (EGF‐R) is a common event in neoplastic transformation and has been shown to be associated with melanocytic tumor progression. Modulation of such a receptor by pharmacological agents could therefore be of clinical interest. We have studied EGF‐R expression, its response to epidermal growth factor (EOF) and modulation effects by interferon gamma (IFNγ) on human melanoma cells. Addition of EOF, anti‐EGF and anti‐EGF‐R antibodies had no effect on proliferation of six melanoma cell lines tested. We report in this communication that EGF‐R expression on human melanoma cells can be modulated by IFNγ. In the melanoma cell lines treated with IFNγ. proliferative behavior was not affected; however, we demonstrate a downregulation of EGF‐R expression on the protein level, by immunohistochemistry and flow cytometric analysis, and an accumulation of EGF‐R mRNA by Northern blot analysis. The results suggest that IFNγ downregulates EGF‐R expression at a posttranscriptional level on human melanoma cells. This EGF/EGF‐R interaction and its modulation by IFNγ on human melanoma cells needs to be further clarified regarding itsin vivosignificance for the treatment and prognos