In this report, we present the first regional quantitative analysis of age-related differences in the heritability of cortical thickness using anatomic MRI with a large pediatric sample of twins, twin siblings, and singletons (n 5 600, mean age 11.1 years, range 5–19). Regions of primary sensory and motor cortex, which develop earlier, both phylogenetically and ontologically, show relatively greater genetic effects earlier in childhood. Later developing regions within the dorsal prefrontal cortex and temporal lobes conversely show increasingly prominent genetic effects with maturation. The observation that regions associated with complex cognitive processes such as language, tool use, and executive function are more heritable in adolescents than children is consistent with previous studies showing that IQ becomes increasingly heritable with maturity (Plomin et al.[1997]: Psychol Sci 8: 442–447). These results suggest that both the specific cortical region and the age of the population should be taken into account when using cortical thickness as an intermediate phenotype to link genes, environment, and behavior. Hum Brain Mapp 30: 163–174, 2009.