The expression of neurotransmitter receptors on the surface of immunocompetent cells is generally accepted as evidence that the nervous system can influence immune responses, even though many aspects of these interactions remain to be elucidated. In this article, we analyzed the expression of the alpha3 nicotinic receptor subunit in human cell lines of myeloid and lymphoid origin and show that the alpha3 mRNA and the receptor molecules containing this subunit are specifically expressed in T lymphocyte cell lines. We have previously characterized the structural properties of the human alpha3 nicotinic subunit gene promoter and defined its functional profile in neuronal cells; in this study, we analyzed the activity of the alpha3 promoter in T lymphocytes and found that the same minimal promoter located in the 0.16-kb BglII-AccIII fragment is responsible for the expression of the alpha3 mRNA in both neuronal and T lymphocyte cell lines. However, the alpha3 transcription initiation patterns in the two cell types were both qualitatively and quantitatively different, and the minimal promoter was differentially modulated by downstream and upstream regulatory elements. These findings suggest that distinct transcriptional mechanisms allow the same promoter to be regulated in a tissue-specific fashion, according to the different functional needs of the two cell types.