Numerous publications confirm the efficacy of intranasal administration for the delivery of compounds and cells to the CNS with the added benefit of minimal systemic spread. Various strategies have been employed in an effort to increase uptake such as nanoparticles and PEGylation; however, the intranasal pathway is so efficient these had minimal effect or were negated by optimizing the ionic strength of the buffer used. Not all studies have had a successful treatment effect despite high CNS concentrations of the compound administered. This illustrates an important caveat, the intranasal pathway is not a cure-all for CNS Geldanamycin-Biotin disease, but it is a highly efficient means of delivering PKI-166 agents that may or may not have their own unique target and mechanism. Prior studies hypothesized the pathway taken to the CNS following intranasal administration to be a combination of the olfactory and trigeminal nerve. However, a literature search failed to produce any studies that used a physical transection of the proposed paths to demonstrate loss of transport into the CNS. This study shows that using intranasal administration, transection of the RMS decreases CNS concentrations of radio-labeled peptides by over 80%. This suggests that the RMS is the major pathway used following intranasal administration. The intranasal pathway could provide an inexpensive, noninvasive, and effective means of gaining high concentrations of agents in the CNS without systemic side effects. This pathway could be applied to the treatment of many conditions including traumatic brain injury, stroke, and neurodegenerative disease. This study has provided evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs may contribute to the development of therapeutics tailored for efficient transport within this structure. The transport capacity of the RMS is likely to be influenced by the physiochemical properties of administered substances such as molecular weight, solubility, charge and dissociation characteristics.