The oncogenic potential of translation initiation factors (eIF-4E and eIF-2alpha) has been described in previous studies leading to the definition of translational oncogenes. Two previously isolated cDNA clones, expressed differently in human melanoma cells and normal human melanocytes, were identified in this study as coding for the translation initiation factor eIF-4A1. Northern-blot analysis revealed consistent overexpression of eIF-4A1 mRNA in a panel of 14 melanoma cell lines (on an average 5.6 times higher than in cultures of normal human melanocytes). In contrast, the mRNAs of the other group-4 translation initiation factors (eIF-4A2, eIF-4B, eIF-4E and eIF-4gamma) were less and not consistently elevated. Cultures of congenital melanocytic nevi exhibited intermediate expression of eIF-4A1. Thus, eIF-4A1 overexpression seems to be an important feature of melanoma cells and might contribute to their malignant transformation.