The hck gene encodes a src-like protein-tyrosine kinase that is expressed predominantly in cells of myeloid origin. To examine the molecular basis of hck expression, we have cloned and characterized the murine hck gene and defined a set of transcriptional regulatory sequences. Transcripts from the hck gene have heterogeneous 5' ends, with one major and several minor transcriptional start sites. The promoter lacks a TATA-like sequence, but has three Sp-1 and two AP-2 binding sites. Constructs containing 2.5Kb or 0.6Kb of sequence 5' to the major transcription start site were capable of directing expression of a reporter gene transfected into fibroblasts. Expression of the former construct, but not the latter, was inducible with LPS. We conclude that LPS induction of hck transcripts, previously demonstrated in myeloid cells, results from the presence of an LPS-responsive element located within the hck promoter.