The author has recently reported the distribution of the cytoskeleton-associated protein caldesmon in spleen and lymph nodes detected with different antibodies against caldesmon (J Histochem Cytochem 58:183-193, 2010). Here the author reports the distribution of caldesmon in the CNS and ganglia of the mouse using the same antibodies. Western blot analysis of mouse brain and spinal cord showed the preponderance of l-caldesmon and suggested at least two l-caldesmon isoforms in the brain. Immunostaining revealed the predominant reactivity of smooth muscle cells and cells resembling pericytes of many large and small blood vessels, ependymocytes, and secretory cells of the pineal gland and pituitary gland. Neuronal perikarya and neuropil in general displayed no or weak immunoreactivity, but there was stronger labeling of neuronal perikarya in dorsal root and trigeminal ganglia. In the brain, staining of the neuropil was stronger in the molecular layers of the dentate gyrus and cerebellum. Results show that caldesmon is expressed in many different cell types in the CNS and ganglia, consistent with the notion that l-caldesmon is ubiquitously expressed, but it appears most concentrated in smooth muscle cells, pericytes, epithelial cells, secretory cells, and neuronal perikarya in dorsal root and trigeminal ganglia.