Colony-stimulating factor-1 (CSF-1 or M-CSF) is required for the growth and differentiation of macrophage progenitors, and for the survival of mature macrophages. Expression of the CSF-1 gene in monocytes and fibroblasts is controlled at both the transcriptional and post-transcriptional levels. To study the molecular mechanisms which mediate changes in CSF-1 expression, the 5' promoter region of the mouse CSF-1 gene was cloned. A high degree of structural and sequence similarity between the mouse and human CSF-1 genes was observed. A transcription start point was located 182 bp upstream from the start codon. Several sequences homologous to known cis-acting elements were identified in the 5'-flanking region. The CSF-1 promoter region was able to direct expression of a linked reporter gene in C3H10T1/2 mouse embryo fibroblasts. Deletion in the CSF-1 promoter region between bp -774 and -629 resulted in a significant decrease in promoter activity. The identification of a functional promoter for CSF-1 will serve as a valuable tool for studying the regulation of CSF-1 expression.