AbstractRecent studies have suggested that sex‐specific genetic architecture could be because of the effects of autosomal genes that are differentially expressed in males and females. Yet, few studies have explored the effects of X‐linked genes on sex‐specific genetic architecture. In this study, we extended the variance component, maximum likelihood method to evaluate the relative contributions of sex‐specific effects on both autosomes and the X chromosome to estimates of heritability of 20 quantitative human phenotypes in the Hutterites. Seventeen of these traits were previously analyzed in this population under a model that did not include X chromosomal effects; three traits are analyzed for the first time (age at menarche, percent fat and fat‐free mass [FFM]). Seven traits (systolic blood pressure (SBP), adult height, fasting insulin, triglycerides, lipoprotein (a) [Lp(a)], serotonin, and age at menarche) showed significant X‐linked effects; three of these (SBP, adult height, and triglycerides) showed X‐linked effects only in males. Four traits (Lp(a), low‐density lipoprotein cholesterol, ratio of percent predicted forced expiratory volume at 1 s/forced vital capacity, and FFM) showed significant sex‐environment interactions, and two traits (high‐density lipoprotein cholesterol and FFM) showed significant sex‐specific autosomal effects. Our analyses demonstrate that sex‐specific genetic effects may not only be common in human quantitative traits, but also that the X chromosome both plays a large role in these effects and has a variable influence between the sexes. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.