A gene responsible for a non-specific form of X-linked mental retardation (MRX19) was localised by linkage analysis. Exclusions and regional localisation were made using 21 highly informative PCR-based markers along the X chromosome. Significant lod scores at a recombination fraction of zero were detected with the marker loci DXS207, DXS987 (Zmax = 3.58) and DXS999 (Zmax = 3.28) indicating that this gene is localised to the proximal portion of Xp22. Recombination between MRX19 and the flanking loci KAL and DXS989 was observed. The multipoint CEPH background map, with map distances in cM, is DXS996-1.8-KAL-19.0-DXS207-0.9-[DXS987,DXS443 ]-4.3-DXS999-3.5-DXS365-14.0-DXS989. Two other MRX disorders and two syndromal mental retardations, Coffin-Lowry syndrome and Partington syndrome, have been mapped to this region. There is a possibility that the 3 MRX disorders are the same entity. Most MRX disorders remain clustered around the pericentromeric region.