The response of the lower oesophageal sphincter (LOS) to intragastric instillation of protein was assessed in 10 healthy volunteers. Sphincter pressures were measured by a rapid pull-through technique and serum gastrin concentrations during each test were determined by radioimmunoassay. Despite stimulation of gastrin release by protein instillation, no significant change in LOS pressure was observed. However, intravenous pentagastrin (0.25 and 0.5 microgram/kg) produced an immediate increase in sphincter pressure, which then returned to the basal level within four minutes. Thus, although pentagastrin is an effective pharmacological stimulant of the sphincter, endogenous gastrin appears not to be a physiological determinant of LOS pressure in man.