The present report elucidates the movement of 201Tl through the cerebrospinal fluid compartment and its subsequent uptake by normal brain. Autoradiographic studies of rat brain, after stereotaxic 201Tl injection into either the lateral or fourth ventricle, reveal that 201Tl moves freely through the cerebrospinal and extracellular fluid compartments. Subsequent to lateral ventricular injection, central thalamic and specific hypothalamic nuclei are heavily labeled. Densely labeled mesencephalic nuclei include the periaqueductal grey and oculomotor nuclear complex. Labeling of giant cells within the vestibular complex is suggestive of neuronal uptake. Major fiber tracts are devoid of label confirming that 201Tl uptake does not occur in white matter. Most labeling following fourth ventricle injection occurs within the caudal medulla and cervical spinal grey. Our findings suggest that 201Tl uptake by normal brain from the cerebrospinal fluid occurs as a function of thallium concentration and neuronal activity.