The effect of chronic total sleep deprivation (TSD) on the regulation of central noradrenergic receptors was evaluated. Rats were subjected to 10 days of TSD by the disk-over-water method. As in previous TSD studies, these rats showed greater increases in food intake and energy expenditure and greater eventual declines in waking body temperature than their yoked-control (TSC) rats. After sacrifice, alpha 1-, alpha 2-, and beta-adrenoceptors were determined in 11 brain regions using radioligand binding assays with [3H]prazosin, [3H]rauwolscine, and 125I-iodocyanopindolol, respectively. Adrenoceptor density and affinity values were significantly different among TSD, TSC, and normally caged control rat groups only for the cerebellum, which showed higher alpha 2-binding density concomitant with lower affinity and lower beta-binding density than cage control rats. Such changes are attributable to apparatus or stimulus effects common to TSD and TSC rats. Given the absence of firm evidence for a TSD-induced downregulation of central noradrenergic receptors, the present results offer no support for the hypothesis of Siegel and Rogawski that a major function of paradoxical sleep is to upregulate these receptors.