Cerebrospinal fluid-contacting (CSF-c) cells are found in all vertebrates but their function has remained elusive. We recently identified one type of laterally projecting CSF-c cell in lamprey spinal cord with neuronal properties that expresses GABA and somatostatin. We show here that these CSF-c neurons respond to both mechanical stimulation and to lowered pH. These effects are most likely mediated by ASIC3-channels, since APETx2, a specific antagonist of ASIC3, blocks them both. Furthermore, lowering of pH as well as application of somatostatin will reduce the locomotor burst rate. The somatostatin receptor antagonist counteracts the effects of both a decrease in pH and of somatostatin. Lateral bending movement imposed on the spinal cord, as would occur during natural swimming, activates CSF-c neurons. Taken together, we show that CSF-c neurons act both as mechanoreceptors and as chemoreceptors through ASIC3 channels, and their action may protect against pH-changes resulting from excessive neuronal activity.