Equine dysautonomia (grass sickness) is a frequently fatal disease of horses characterised by intestinal stasis. Interstitial cells of Cajal (ICC) are the pacemakers and mediators of neurotransmission in the gastrointestinal tract. Impaired ICC-mediated control of motility has been implicated in intestinal disorders in laboratory mammals, humans and in equine grass sickness The aim of this study was to compare the in vitro electrical properties of ileum from grass sickness cases with horses free from gastrointestinal disease. Intracellular microelectrode recordings were made from smooth muscle cells in cross-sectional preparations of equine ileum, superfused in vitro. Samples were taken from six horses with grass sickness and from eight horses free from gastrointestinal disease, all euthanised on humane grounds Ileal tissues were processed for haematoxylin and eosin histology, and c-Kit immunohistochemistry. Membrane potential oscillations were recorded in the ileal preparations from four of the six horses with grass sickness and from all of the normal horses. A waxing and waning pattern of the membrane potential oscillation activity was noted in some cells. In comparison to the normal horses, the membrane potential oscillations in grass sickness horses had a significantly reduced frequency (P=0.0001) and increased duration (P=0.0002). Immunohistochemistry revealed the presence but reduction of ICC in grass sickness. Histological assessment of the same tissues used for analysis of the ICC showed the depletion and pathology of the enteric neurons in grass sickness. Therefore, the majority of ileal preparations from grass sickness-affected horses exhibited prominent membrane potential oscillation activity suggesting that, although the neural elements are damaged severely, the ICC-mediated pacemaker function remains intact. (C) 2002 Elsevier Science B.V. All rights reserved.