The brain is protected against invading pathogens by the blood-brain barrier, and also by its own innate defence system consisting of microglia and neurons in a coordinated network. Antimicrobial peptides are a part of the innate immune system at epithelial surfaces, and may also have important functions in the brain. Recently, we characterized the rat homologue of the human cathelicidin LL-37, designated rCRAMP. Here we present several lines of evidence for this peptide being expressed in rat CNS. (1) A peptide/protein extract of rat brain is active against bacteria in a salt-dependent manner. (2) Western blot analysis demonstrates the presence of rCRAMP in rat brain extract. (3) rCRAMP peptide and mRNA are present mainly in specific CNS regions (olfactory bulb, cerebellum, medulla oblongata and spinal cord). (4) rCRAMP-like immunoreactivity is detected in olfactory bulb, cerebellum and spinal cord by immunohistochemistry. (5) Moreover, the transcript of rCRAMP is detected in primary cultures from hippocampus, striatum, cerebellum and spinal cord, as shown with RT-PCR and Southern blot analyses. In addition, the rCRAMP peptide exhibits in vitro activity against the neuropathogenic bacterium Neisseria meningitidis. Taken together, these data suggest that the cathelicidin rCRAMP may play a role in the innate immunity of the CNS.