Background: The therapeutic effect of drugs inhibiting acid production on acid-related discomforts is related to both the onset and duration of action of the drug. The effects on gastric pH by single oral doses of some acid-inhibiting drugs were investigated by measuring daytime (morning to lunch) intragastric pH in healthy volunteers. Methods: This randomized, single-dose, 4-way crossover study included 15 healthy fasting subjects. Effervescent ranitidine tablets 150 and 300 mg, fast-dissolving famotidine tablets 20 mg and capsules of omeprazole 20 mg were administered. Measurements of intragastric pH were performed every 4 s for 10 min prior to drug administration and during the following 4 h. Results: The effervescent ranitidine tablets (150 or 300 mg) produced similar changes in intragastric pH: following an immediate increase to about pH 5, intragastric pH decreased slightly over the next 10-20 min. Thereafter pH increased steadily, reaching pH 4 after 20-40 min and pH 6 after about 70 min. After famotidine, pH 4 was reached after 80 min, significantly slower than ranitidine. After omeprazole, pH 3 was never reached. Ranitidine 150 and 300 mg showed significantly larger integrated pH responses over the 4-h observation period, compared to famotidine (P = 0.0288 and 0.0074) or omeprazole (P < 0.001). Conclusions: After single-dose administration to healthy fasting volunteers), ranitidine effervescent tablets showed a significantly more rapid onset of action and a significantly larger integrated pH response compared to either famotidine 20 mg fast-dissolving tablets or omeprazole 20 mg capsules.