Non-specific mental retardation (MR) is a condition in which MR appears to be the only consistent manifestation. The X linked form (MRX) is genetically heterogeneous. We report clinical, cytogenetic, and linkage data on a family with X linked non-specific MR. Two point and multi-point linkage analysis with 18 polymorphic markers, covering the entire chromosome, showed close linkage to DXS1001 and DXS425 with a maximal lod score of 2.41 at 0% recombination. DXS178 and the gene for hypoxanthine phosphoribosyl-transferase (HPRT), located in Xq22 and Xq26 respectively, flank the mutation. All other chromosomal regions could be excluded with odds of at least 100:1. To our knowledge there is currently no other non-specific MR gene mapped to this region. Therefore, the gene causing MR in this family can be considered to be a new, independent MRX locus (MRX35).