The autism spectrum disorders (ASDs) and fragile X syndrome (FXS) share many symptoms such that many fragile X males will meet autism diagnostic criteria at some point in their lives. Whereas other forms of autism appear to involve multiple genetic factors, FXS is caused by mutations in a single gene, FMR1, that lead to loss of the protein it encodes, FMRP. Thus, genetic models of FXS facilitate the study of the role of FMRP in addition to offering insights into mechanisms underlying symptoms shared with the ASDs. While most studies have focused on the effect of FMRP deletion on neuronal physiology, very little is known about its role in glial development. Two studies suggest that FMRP suppresses the synthesis of myelin basic protein (MBP), indicating that loss of FMRP may lead to alterations in myelination. Consistent with this possibility, human imaging studies have revealed abnormalities in the microstructure of white matter tracts in FXS and the ASDs. One possible consequence of abnormal myelination is the impairment of action potential propagation, potentially leading to alterations in the timing of synaptic signaling, a key regulator of spike-timing dependent plasticity (STDP). In support of this notion, global Fmr1 knockout (Fmr1-/y) mice have alterations in this form of synaptic plasticity. Myelination in the rodent CNS begins around postnatal day 14 (P14) and reaches its maximum around P35. To determine whether loss of FMRP affects the development of forebrain myelinated fibres, we compared the progression of myelination in Fmr1-/y mice and wild-type littermates over this period. We used immunohistochemistry for MBP to determine the gross morphology of major white matter tracts at P15 and P21. To get a functional and structural index of axon myelination, we quantified the g-ratios from myelinated axons in high-power electron micrographs through the corpus callosum at P14 and P35. Finally, to understand how loss of FMRP might affect the basic physiological properties of axons, we simulated axon conductance velocity using measures derived from our quantification of electron micrographs. Our preliminary data suggest that loss of FMRP does not affect the gross morphology of white matter tracts or g-ratio measures. However, axon diameter is significantly larger in Fmr1-/y mice (n = 5) compared to controls (n = 4) at P35 (p = 0.03; Student’s t-Test). We will further use our computer simulations to test whether this increase in axon diameter would eventually lead to altered signal transduction or not. Together, our current data suggest a potential mechanism underlying the disrupted STDP associated with the loss of FMRP, and offer a new perspective on the cause of intellectual disabilities in FXS and related disorders.