The effects of niperotidine, a novel histamine H2-receptor antagonist, on nocturnal gastric acid secretion in healthy volunteers, have been investigated. Twenty subjects were randomly assigned to the placebo (M:F = 7:3; Age 34 +/- SD3 yrs) or to the niperotidine-treated group (M:F = 7:3; Age: 37 +/- 6 yrs) in which 460 mg were administered at 22.00. Intragastric acidity was assessed by means of 24-hour pH-measurement (10.00-22.00) using sensitive antimony monocrystalline electrodes. The percentage of daytime gastric acidity (prandial and interprandial) was similar in both groups (median; interquartile range): placebo group 87.5; 69.5-90.1 vs niperotidine 85.8; 59-89.1. Niperotidine increased the intragastric pH during the period 22.00-10.00. The percentage of time above pH 4 was higher in the treated group (28.4; 14.8-50.7% vs 7.4; 1.4-10.7%; p less than 0.02). The duration of niperotidine action was 5 to 7 hours. The nocturnal pH frequency curve after niperotidine was shifted toward alkaline values with a decrease of acidity in the pH range 1-2 (p less than 0.04). We conclude that a bedtime dose of niperotidine inhibits nocturnal gastric acid secretion in healthy subjects.