This unit describes linkage analysis, an invaluable tool in mapping human disease genes. Linkage analysis is one of several methods used to map genes. Specifically, in linkage analysis cosegregation of two or more genes (traits) is examined in a family unit to determine if they segregate independently according to Mendel's laws or if they do not segregate independently because of their close physical proximity. The procedures outlined in this unit are not always straightforward, and a number of caveats are presented in the commentary regarding possible complications and confounding factors that may arise. Specific examples are given, but it is not possible to cover all possible scenarios or variables. The intention is to enable the reader to master basic principles used in the linkage approach and thus be in a position to undertake, with proper consultation, a linkage-analysis study. This unit deals specifically with lod score analysis in Mendelian disorders.