Using both empirical and simulated data, this study examines selected computational approaches and algorithms for analyzing the genetic etiology of a disease. It compares a wide variety of analytical methods and highlights areas of substantive interest to geneticists investigating human disease. Its methodologic emphasis provides useful guidance for the design of future studies to map disease susceptibility loci. In the first section, a group of experts investigate a multipoint mapping problem by analyzing data that encompass chromosome marker 7 information on cystic fibrosis families. Existing methodologies and computer programs for multipoint mapping are compared and contrasted under the constraints imposed by real human data. In assessing alternative approaches to complex mapping problems, theoretical as well as empirical contributions are considered. The remainder of the volume examines simulated data that comprise two distinct problem sets in which disease and marker loci both are segregating. Here, experts compare methods of linkage analysis that rely only upon data collected on affected individuals.