The "housekeeping" sodium/hydrogen exchanger, NHE1, mediates the electroneutral 1:1 exchange of Na⁺ and H⁺ across the plasma membrane. NHE1 is ubiquitous and is studied extensively for regulation of pH _i, cell volume, and response to growth factors. We describe a spontaneous mouse mutant, s low-w ave e pilepsy, (swe), with a neurological syndrome including ataxia and a unique epilepsy phenotype consisting of 3/sec absence and tonic-clonic seizures. swe was fine-mapped on Chromosome 4 and identified as a null allele of Nhe1. Mutants show selective neuronal death in the cerebellum and brainstem but otherwise are healthy. This first example of a disease-causing mutation in an Nhe gene provides a new tool for studying the delicate balance of neuroexcitability and cell survival within the CNS.