Association and transmission/nontransmission analyses were used in a split sample design to identify disease susceptibility alleles at two loci. Sib-pair analysis on various subsets of the data identified an additional four regions that yielded signals of disease predisposing quantitative trait loci (QTLs). Three of these four regions represented Type I errors. A new simulation indicates that a multiplex sampling strategy would substantially improve QTL detection for this oligogenic transmission model. © 1995 Wiley-Liss, Inc.