Delayed acquisition of developmental motor and cognitive milestones is a common clinical expression of many etiological processes. Imaging exams of developmentally delayed children often show no structural brain alterations despite suspicion of brain maturation delay. MRI studies increasingly suggest that white matter myelination finely reflects the progression in functional brain maturation. In this volumetric MRI study, we sought to evaluate whether developmental delay in children with normal conventional MRI exams is associated with reduced myelinated white matter. A total of 100 children (mean age, 4.4 years) with developmental delay and 50 normally developing age-matched control children underwent 3-D MRI to measure the volume of myelinated white matter. Patients showed a significant reduction in the relative content of myelinated white matter (accounting for 19.8% of brain volume in patients and 21.4% in control subjects, P = 0.005). The observed difference was equivalent to a 3.2-year myelination delay. Although the whole hemispheres were invariably symmetrical, the volume of myelinated white matter was asymmetrical in 30% of patients and 10% of control subjects (P = 0.006). We conclude that volumetric assessment of white matter may reveal a reduction in brain myelination beyond early childhood in developmentally delayed children showing normal brain appearance. This finding further emphasizes the view of white matter myelination as an indicator of functional brain maturation.