Dyslexia is usually defined as persistent difficulty in reading and spelling in the absence of any neurologic or other causes, in an individual with normal intelligence and adequate schooling. Difficulties in spelling and decoding may persist through adult life. The prevalence may be as high as 5-10%, but these figures probably include many types of learning disorders. Currently, there is no single test which permits a clear diagnosis of dyslexia. Over the last 15 years, possible localizations of genes for dyslexia have been reported on chromosome 15(DYX1), 6p21.3-23(DYX2), and 1p. We have investigated a large Norwegian family in which dyslexia is inherited as an autosomal dominant trait. A genome-wide search for linkage was initiated in 36 of the 80 family members and a region in 2p15-p16 was identified which cosegregated with dyslexia. Maximum lod scores of 3.54, 2.92 and 4.32 for three different diagnostic models were obtained. These results were confirmed by a non-parametric multipoint GENEHUNTER analysis in which the most likely placement of the gene was in a 4 cM interval between markers D2S2352 and D2S1337. Haplotype analysis showed that reading disability in this large kindred was due to another cause (most likely ADHD) in 2 children,. This is the first genome search that has been carried out in dyslexia. Isolation of DYX3 will give a new and exciting insight into the processes involved in reading and spelling.