The effect of two doses (37.5 mg/hr and 50 mg/hr) of continuously infused cimetidine on gastric acid secretion and pH control over 24 hours was compared with that of placebo in 21 adult males with active duodenal ulcer or scarring from healed duodenal ulcer. This single-center, double-blind, three-way crossover trial consisted of three treatment periods separated by 5- to 7-day washout periods. Gastric contents were continuously aspirated through a nasogastric tube during the second half of each study hour. Volume, pH, and titratable acidity were measured from the aspirates collected during the last 20 minutes of each aspiration period. The median pH, volume (ml), and titratable acidity (mEq/hr) values for the 37.5-mg/hr infusion were 5, 16.0, and 0.24, respectively (P < 0.05 versus placebo). For the 50-mg/hr infusion, the respective values were 5.3, 15.8, and 0.14 (P < 0.05 versus placebo); and for placebo, the values were 1.4, 30.5, and 6.83. The median percent of time that the pH was > or = 4 was 65%, 65%, and 0% for the 37.5-mg/hr, 50-mg/hr, and placebo infusions, respectively (P < 0.05 versus placebo). The 37.5-mg/hr and 50-mg/hr intravenous doses of continuously infused cimetidine are commonly used in the hospital setting to treat intractable ulcers or prevent upper gastrointestinal bleeding in critically ill patients. The results of this study demonstrate that both doses are similarly effective in maintaining intragastric pH and acid secretion at levels generally recognized as being effective.