We prospectively evaluated autonomic function in 50 patients with clinical and manometric features of a neuropathic form of chronic intestinal pseudo-obstruction (CIP). In 26 patients, there were underlying disease processes that may have affected extrinsic neural control to viscera: diabetes mellitus (n = 16), previous gastric surgery (n = 5), and other neurologic disorders (n = 5). Our aim was to characterize autonomic function in these patients, and those 24 with CIP unassociated with a known underlying neurologic disorder (idiopathic group). We assessed vagal function and sympathetic cholinergic and adrenergic function by means of standardized autonomic tests and quantitated postprandial antral pressure activity. We also measured postprandial levels of pancreatic polypeptide and neurotensin as indicators of vagal function and of the delivery of nutrients to the distal small bowel. Among the idiopathic group (n = 24), two had evidence of a generalized sympathetic neuropathy and five abdominal vagal dysfunction (one had both). Among diabetic patients, three had sympathetic adrenergic failure, six had orthostasis with normal plasma noradrenaline, ten had signs of generalized sympathetic neuropathy and eight had abdominal vagal dysfunction. Vagal dysfunction was identified in all three patients who underwent vagotomy as part of their previous gastric surgery. In the other neurologic syndromes, vagal function was abnormal in three of the five patients. Thus, autonomic and, particularly, vagal dysfunction are confirmed in a majority of patients with CIP associated with known diabetes or neurologic disorders; however, a previously unrecognized autonomic (chiefly vagal) neuropathy of undetermined cause has been identified in five of the 24 'idiopathic' CIP patients.