We have examined the power of linkage detection in pedigrees under a wide range of two-locus models using simulation. Single locus lod score analyses are as powerful for detecting linkage as are two-locus lod score analyses, as long as the mode of transmission (dominant or recessive) of the linked locus is correctly specified. The lod score method is more powerful for detecting linkage in pedigrees than are the various non- parametric statistics. The usefulness of methods that allow for simultaneous linkage analysis to more than one region of the genome are being examined in our bipolar pedigree linkage study. These methods include two-disease-locus, two- marker-locus lod score analysis and heterogeneity models involving multiple unlinked marker loci.