The clinical course, diagnosis, and treatment of 2 patients with acquired intestinal aganglionosis without other neurological involvement or neoplasia are described. They initially presented with constipation and abdominal pain in late childhood. They were found to have enteric ganglionitis with a loss of neurons together with vacuolated nerve cells surrounded by CD3- and CD4-positive T lymphocytes. This process initially affected only the colon but later the entire gastrointestinal tract was involved in 1 patient. Associated with this process there were circulating immunoglobulin G class enteric neuronal antibodies in high titer (1:5000-8000). The staining of central nervous system neuronal nuclei and Western blotting indicated the presence of antineuronal nuclear protein antibodies of the ANNA-1 (anti-Hu) type usually associated with paraneoplastic sensory neuropathy. However, the reaction pattern in enteric neurons was quite different with strong reaction to perikarya and only weak staining of nuclear antigens.