Meprins, membrane-bound oligomeric metalloendopeptidases, contain alpha and/or beta subunits. Their activities have been found in the mouse and rat kidney. The cloned cDNA for the mouse alpha subunit of meprin A (EC cloned cDNA for the mouse alpha subunit of meprin A (EC 3.4.24.18) was used here to survey mRNA expression in kidney of different mouse strains and in various tissues of mice and rats. A single message of 3.6 kilobases was found in kidney of random bred (ICR) and inbred mice (C57BL/6, DBA/2) that contain high meprin A activity and in Sprague-Dawley rat kidney. The alpha subunit message was undetectable in the kidney of C3H/He and CBA mice, inbred strains that do not express meprin A activity. Therefore, meprin A activity in the kidney of mouse strains correlates with the amount of alpha subunit mRNA present. The 3.6-kilobase mRNA meprin alpha subunit message was also detected in the small intestine of the rat but not in mice. No message was detected in brain, heart, skeletal muscle, liver, lung, or spleen of mice or rats. Polymerase chain reaction amplification or Southern blot analysis of genomic DNA revealed that the gene for the alpha subunit is present in all mouse strains as well as in human, monkey, rat, mouse, dog, cow, rabbit, and chicken, but it was not detected in yeast. There is one gene copy present in the mouse genome. The gene was localized to mouse chromosome 17 centromeric to the major histocompatibility complex (H-2) by the interspecific backcrossing method. The localization of this allele to Mep-1, the gene previously found to regulate the expression of meprin A activity in mice, supports the proposal that Mep-1 is the structural gene for the alpha subunit.