Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is involved in the pathogenesis of several human CNS disorders. The AU-rich element (ARE) in the 3'-untranslated region (UTR) of TNF-alpha mRNA is implicated in post-transcriptional control of TNF-alpha. In this study, we showed that a human neuronal ELAV-like protein binds to the ARE in the 3'-UTR of TNF-alpha mRNA. The protein binds to the uridine stretch in AUUUA pentanucleotides inside the ARE in the 3'-UTR of TNF-alpha mRNA. The TNF-alpha mRNA-binding region in the protein appears to be identical to the c-myc and IL-3 mRNA-binding regions. Moreover, this study showed that in vitro treatment of neuroblastoma cells with interleukin-4 (IL-4), which inhibits TNF-alpha production, reduced the expression of the neuronal ELAV-like proteins. These results suggest that the expression of neuronal ELAV-like proteins may be closely associated with the expression of TNF-alpha in neuronal cells.