The recent completion of the Human Genome Project provides the potential to advance our knowledge of pathogenesis and identify the gene(s) associated with particular diseases. However, using human DNA to correlate individual genomic variations with particular disorders such as stroke will be extremely challenging because of the large number of variables within an individual, and across different populations. Mutant animal models of stroke such as the stroke-prone spontaneously hypertensive rat (SHRSP) provide the scientist with genetic homogeneity, not possible within a human population, to aid our search for causative genes. This chapter describes the methods our group have employed to study the genetic heritability of stroke sensitivity in the SHRSP. Sections are included on quantitative trait loci, mapping, and congenic strain construction for the identification of genetic determinants of stroke sensitivity in the SHRSP.