OBJECTIVE: Disorders of colonic motility, such as severe constipation and pseudo-obstruction, remain difficult to treat. The pathophysiology of these conditions is not completely understood, but previous studies suggest a deficiency of cholinergic innervation and an imbalance in autonomic regulation of colonic motor function as contributing factors. Therefore, increasing the availability of acetylcholine in the bowel wall with a cholinesterase inhibitor, such as pyridostigmine, may improve symptoms. METHOD: We studied thirteen patients with severe constipation (slow transit type) or recurrent pseudo-obstruction. The six patients with slow transit constipation had mechanical obstruction and pelvic floor dysfunction excluded, and normal calibre colon and slow transit confirmed. These patients were offered pyridostigmine in an attempt to avoid surgery. The seven patients with pseudo-obstruction had dilated bowel on imaging, and mechanical obstruction was excluded. These patients received pyridostigmine when symptoms recurred, despite previous treatments. Pyridostigmine was initiated at 10 mg b.i.d. and increased if required. RESULTS: One of the six patients with slow transit constipation reported improvement of symptoms and had concurrently weaned anti-psychotic medications. Pyridostigmine was ceased in the remaining five patients due to lack of efficacy and/or side effects. Four patients proceeded to surgery for refractory symptoms. All seven patients with pseudo-obstruction had some improvement of symptoms with few side effects. Of these, two later had surgery for recurrent symptoms. CONCLUSION: In patients with slow transit constipation, treatment with pyridostigmine does not improve symptoms. However, it does improve symptoms in patients with recurrent pseudo-obstruction with few side effects, offering an extra treatment option for these patients.