The chicken lysozyme gene is constitutively expressed in macrophages and controlled by steroid hormones in the oviduct. We have investigated the influence of the 5' noncoding region of this gene on its cell-specific transcriptional activation. In transient transfection experiments we have identified a far-upstream cell-specific enhancer element 6.1 kb 5' to the transcriptional start site of the lysozyme gene. Transcription from the lysozyme gene promoter is induced by this element in a position- and orientation-independent manner in lysozyme-producing myeloid cells (HBCI), but not in non-producing chicken embryo fibroblasts (CEF-38). The enhancer region correlates with a DNase-hypersensitive chromatin site which is only detectable in cells of tissues in which the lysozyme gene is transcribed. We suggest that this far-upstream element is involved in the tissue-specific control of lysozyme gene activity.