Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling. Little is known of the distribution and function of the cyclic adenosine monophosphate (cAMP) hydrolyzing PDE8A family. Employing immunohistochemistry and Western blots this study maps the distribution of PDE8A in the brain of adult male Sprague-Dawley rats and in the trigeminal ganglion. PDE8A was confined to neuronal perikaryal cytoplasm and to processes extending from those perikarya. The neurons exhibiting PDE8A-immunoreactivity were widely distributed in the forebrain, brain stem, and cerebellum. Strongly immunoreactive neurons were located in the olfactory bulb, the septal area, zona incerta, and reticular nucleus of the thalamus. Less immunoreactivity was seen in the hippocampus and cerebral cortex. Intense staining was detected in both the substantia nigra and the sensory trigeminal nucleus. In cerebellum PDE8A immunoreactivity was located not only in the Purkinje cells, but also in the granular cells as well as the parallel fibres in the molecular layer. PDE8A immunoreactivity was represented in the epithelial lining of the choroids plexus, the dura mater, and the neurons of the trigeminal ganglion. The localization of the cAMP degrading PDE8A may indicate a role for PDE8A in cAMP signaling related to pain transmission, motor function, cognition and olfaction.