Meprins are kidney and intestinal proteases encoded by two distinct genes, MEP1A and MEP1B. MEP1A was previously mapped to human chromosome 6p, by the use of radiation and somatic cell hybrids, in the region containing the gene for autosomal recessive polycystic kidney disease (ARPKD). We now report the fine mapping of MEP1A using yeast artificial chromosome clones, and linkage analysis of ARPKD families. The results from both physical and genetic mapping exclude MEP1A as a candidate for ARPKD. These studies place MEP1A in a region more telomeric to 6p12 and closer to the HLA loci than previously reported. More specifically, MEP1A is localized between loci D6S272 and D6S282, close to D6S452, on human chromosome 6p21.2-p21.1. The more precise location of MEP1A will facilitate genetic studies of this locus and clarify the relation of this gene to others.