Case summary A 7-year-old neutered male Persian cat was presented for acute vomiting and inappetence. Physical examination revealed severe abdominal distension. Radiographs demonstrated pneumoperitoneum, megaoesophagus and generalised gaseous distension of the digestive tract. Exploratory coeliotomy was performed, revealing markedly distended and thickened small and large intestines with no observable peristalsis. No intestinal perforation was present. Bacteriological and cytological analysis of abdominal fluid revealed a septic peritonitis involving Pasteurella multocida. Full-thickness intestinal biopsies demonstrated lymphocytic ganglioneuritis localised to the enteric nervous system, in association with glandular atrophy and muscular layer hypertrophy. Amoxicillin-clavulanate and analgesics were given. The cat's general condition gradually improved after the addition of pyridostigmine bromide (0.5 mg/kg q12h PO), initiated 3 days postsurgery. Vomiting resolved and did not recur. Follow-up radiographs at 15 days, and 1 and 6 months showed persistent intestinal ileus, milder than on the pretreatment radiographs. Thirty months after presentation the cat is still alive, without clinical signs, and receives 1 mg/kg q12h pyridostigmine. Relevance and novel information To our knowledge, this is the first case of ganglioneuritis of the myenteric plexus described in cats, as well as the first one successfully treated with pyridostigmine. Chronic intestinal pseudo-obstruction is a very rare condition in cats but should be included in the differential diagnosis of generalised gastrointestinal ileus.