We found that administering a fluorescent tracer into the nasal cavity of mice produces high levels of fluorescence throughout multiple regions of the brain, including the hippocampus, cortex and cerebellum. Furthermore, in order to determine the role of the RMS in the uptake of peptides into the brain, we used radiolabeled 125I-EPO and 125I-Calcitonin. In a normal mouse, we found significant quantities of both 125I-cytokines in the brain 20 min after intranasal administration; however, surgical transection of the RMS abolished uptake into the brain. Therefore, we Ki11502 hypothesize that the intranasal pathway could provide a simple, rapid, and non-invasive means of delivering peptides into the brain via the RMS. The intranasal/RMS pathway could be applied to the treatment of many conditions including stroke, traumatic brain injury and neurodegenerative diseases. In the present study the intranasal administration of low molecular weight fluorescent probes and 21H7 radioligands results in accumulation of fluorescence and radioactive signal throughout the brain, but not in peripheral tissues such as lungs and blood. However, when the RMS is surgically transected, the radiolabeled markers are found mainly in the peripheral organs, with no statistically significant quantities in the brain. The volume chosen for administration into the nasal cavity has been shown previously to be the maximum volume that can be applied to the olfactory tissue without subsequent systemic leakage. Therefore, the presence of the radioligands in the peripheral tissue is unlikely due to the volume administered into the nasal cavity. We hypothesize that structural disruption of the RMS prevented uptake into the CNS. This resulted in prolonged contact with the respiratory tissue allowing the radioligands to take another path, resulting in an increase in radioactive signal in the lung and blood samples. We observed an increase in mucosal volume in the nasal cavity after RMS transection. This increase in fluid volume may also contribute to the likelihood that the radioligands are taken up systemically via the circulatory system or aspirated into the lungs.