During modified sham feeding (MSF) the role of endogenous gastric acid secretion and the influences of the autonomic nervous system on the release of pancreatic polypeptide (PP) and gastrin have been studied in 12 healthy subjects (aged 24-38 years). Sham feeding was performed without pretreatment (control) and after pretreatment with 400 mg cimetidine, 80 mg propranolol (both given orally) or 1 mg atropine administered subcutaneously 60 min prior to sham feeding. MSF induced a significant increase (about 100%) in PP release. Its early peak was reduced by pretreatment with propranolol whereas cimetidine had no effect. Atropine completely abolished the PP response. Gastrin release was stimulated by MSF only after prior administration of cimetidine and, to a lesser extent, after atropine pretreatment. It is concluded that: (1) the PP release after stimulation is under strong cholinergic control but is also mediated--particularly in the early phase--by adrenergic mechanisms; (2) endogenously released acid during vagal stimulation plays a minor role in the modulation of PP secretion, but (3) masks gastrin response to MSF.