SUMMARY Lower oesophageal sphincter pressure has been studied in pernicious anaemia patients and controls using an infused open-tipped system. Resting sphincter pressure was significantly (p < 0.01) lower in the pernicious anaemia patients. After gastric acidification with 01 N HCl pressure fell significantly (p < 0.01) in both groups. Following subsequent alkalinization, lower oesophageal sphincter pressure for controls rose significantly (p < 0.001). For pernicious anaemia patients the pressure after alkali was not greater than resting levels. Graded intravenous doses of pentagastrin in controls resulted in a peak pressure change of 38.5 4.9 mm Hg after the 0.8 gg/kg dose. For patients the peak pressure change was only 13.0 5.2 mm Hg and occurred after 0.4 ,ug/kg. Cholinergic stimulation with edrophonium (10 mg) produced a peak pressure change of 20.6 2.6 mm Hg in controls but only 3.5 ± 10 mm Hg in pernicious anaemia patients (p < 0.001). In addition, no change in lower oesophageal sphincter pressure occurred in patients after stimulation with subcutaneous betazole (1.5 mg/kg).In conclusion, the lower oesophageal sphincter in pernicious anaemia is characterized both by a low resting pressure and a decreased response to endogenous and exogenous stimuli. These results suggest a primary end organ defect and most likely indicate abnormal smooth muscle function in pernicious anaemia. Resting sphincter pressure levels and edrophonium response in age-matched subjects indicate that these changes are not due to aging alone.The lower oesophageal sphincter has been shown to respond to varied hormonal and pharmacological stimuli (Giles, Mason, Humphries, and Clark, 1969;Castell and Harris, 1970;Roling, Farrell, and Castell, 1972;Cohen and Lipshutz, 1971;Bettarello, Tuttle, and Grossman, 1965; Resin, Stem, Sturdevant, and Isenberg, 1972). In particular the hormone gastrin has been shown to cause marked increases in pressure in this sphincter (Giles et al, 1969;Castell and Harris, 1970) and recent studies indicate that endogenous gastrin is a major determinant of sphincter tone (Lipshutz, Hughes, and Cohen, 1972). The marked elevation of serum gastrin detected in patients with either pernicious anaemia