We took as our working hypothesis the premise that there could be a single locus of major effect underlying a subset of cases in the simulated Problem 2 data set, and took as our primary goal the task of mapping that locus. Treating the disease as dichotomous and using discriminant function analysis, we were able to separate affected individuals into two disease categories: Disease Type I (DT-I) cases, whose disease was by hypothesis caused by the major locus; and Disease Type II (DT-II) cases, whose disease was by hypothesis produced by other causes. Segregation analysis showed evidence of simple recessive inheritance among the DT-I individuals. Linkage analysis under the best-fitting recessive model gave clear evidence of linkage to D1G2. In the generating model, this marker is linked to a major gene for disease with recombination fraction θ = 0, and the mode of inheritance at that locus is recessive (when the trait is considered as a dichotomy). We conclude that when the true model is complex, focussing on subtypes of disease that show evidence of simple Mendelian inheritance may be a useful first step in determining the underlying model and mapping major genes. © 1995 Wiley-Liss, Inc.