The LDL receptor-related protein (LRP) or alpha 2-macroglobulin receptor (A2mr) is encoded by a 15-kb mRNA in mouse and human. Probes encompassing different regions of the mouse cDNA were used to isolate clones from a cosmid library of mouse strain 129. Four overlapping cosmids were used for restriction mapping and Southern blot analysis. This map and hybridization data obtained with oligonucleotide probes from the 5' and 3' ends of the Lrp cDNA demonstrated that the mouse gene is approximately 85 kb in size. The Lrp promoter region was sequenced and reveals strong evolutionary conservation of putative regulatory elements between mouse and human. The present study will facilitate detailed elucidation of the function of LRP in vivo.