Of the vertebrate senses, touch is the least understood at the molecular level. The similarity of mammalian DEG/ENaC cation channels to nematode proteins involved in mechanotransduction suggested they might be a part of cutaneous mechanosensors. We studied two DEG/ENaC channels, the brain Na+ channel 1 (BNC1) and the dorsal root acid-sensing ion channel (DRASIC). When expressed in heterologous cells, these proteins form acid-activated cation channels, which has suggested that they may play a role in acid-evoked nociception. We found that each protein showed specific localization in several different specialized sensory nerve endings of skin. Their location suggested they might participate in mechanosensation and/or acid-evoked nociception. To test these possibilities, we disrupted the mouse BNC1 and DRASIC genes. Cultured dorsal root ganglion sensory neurons from null animals displayed alterations in acid-gated currents. Disrupting the BNC1 gene markedly reduced the sensitivity of low-threshold, rapidly adapting mechanoreceptors, whereas loss of DRASIC increased the sensitivity of these receptors that detect light touch. The response of acid-stimulated nociceptors was normal in BNC1 null mice. In contrast, loss of DRASIC reduced the sensitivity of a mechanoreceptor responding to noxious pinch, and decreased the response of acid and noxious heat-sensitive nociceptors. The data suggest that these channel subunits participate in heteromultimeric complexes where they serve as central components of cutaneous sensory receptors. The results identify BNC1 as essential for normal cutaneous sensation. Moreover in different cellular contexts, DRASIC may respond to mechanical stimuli or to low pH to mediate normal touch and pain sensation.