OBJECTIVE: Acetylcholine plays a central and peripheral role in regulating gastric motility. In the hypothalamus, it is a key neuroendocrine modulator; acting through somatostatin, it brings about the release of growth hormone (GH). We measured hypothalamic cholinergic receptor sensitivity in patients with nonulcer dyspepsia (NUD) by examining GH release in response to cholinergic challenge. METHODS: Forty patients with NUD and 40 healthy comparison subjects were administered pyridostigmine (the acetylcholinesterase inhibitor, 120 mg), and GH release over a 3-h period was monitored. RESULTS: Calculating response as the maximum GH relative to baseline (delta GH), the mean +/-SEM response in the patients was 11.9 +/- 1.9 U/L and in the healthy subjects 6.7 +/- 0.7 mU/L (t = 2.1, df = 78, p = 0.03). Helicobacter pylori status had no appreciable impact on GH response with H. pylori-positive patients having a mean response of 10.5 +/- 2.1 mU/L and negative patients a mean response of 13.2 +/- 3.4 mU/L. Overall, patients with NUD release more GH in response to pyridostigmine challenge than healthy subjects. CONCLUSIONS: Patients with NUD may have a pathophysiological disturbance involving central cholinergic systems.