Size sexual dimorphism occurs in almost all mammals. In Portuguese Water Dogs, much of the difference in skeletal size between females and males is due to the interaction between a Quantitative Trait Locus (QTL) on the X-chromosome and a QTL linked to Insulin-like Growth Factor 1 (IGF-1) on the CFA 15 autosome. In females, the haplotype of CFA 15 resulting in small size is dominant. In males, the haplotype for large size is dominant. Females, homozygous at the CHM marker on the X chromosome and homozygous for the large size CFA 15 haplotype are, on average, as large as large males. However, all females that are heterozygous at the CHM marker are small, regardless of their CFA 15 genotype. This interaction suggests a genetic mechanism that in turn leads to a scenario for the evolution of size sexual dimorphism consistent with a proposal of Lande that sexual dimorphism can evolve because females secondarily become smaller than males as a consequence of natural selection for optimal size. Our results also can explain Rensch's Rule, which states that size is often positively correlated with the level of size sexual dimorphism.