Adult onset primary open angle glaucoma is a leading cause of blindness throughout the world. The disease results in an apoptotic death of retinal ganglion cells that is usually associated with an elevation of intraocular pressure. Familial aggregation of the disorder provides evidence for strong genetic influences that are likely to be the result of multiple susceptibility genes. A two-stage genome scan to identify the genomic locations of glaucoma susceptibility genes was performed using an initial pedigree set of 113 affected sibpairs and a second pedigree set of 69 affected sibpairs. Linkage analysis was performed using both model-dependent (lod score) and model-independent affected relative pair and sibpair methods. Twenty-five regions identified by the initial scan were further investigated using the second pedigree set. In the combined data analysis, regions located on chromosomes 2, 6, 9, 11, 14, 17 and 19 continued to produce model-dependent lod scores and/or an MLS >1.0, while five regions (2, 14, 17p, 17q and 19) produced an MLS >2. 0. Multipoint analysis using ASPEX also showed significant results on chromosomes 2, 14, 17p, 17q and 19. These results are an important step towards the identification of genes responsible for the genetic susceptibility to this blinding condition.