We conducted a double-blind, placebo-controlled study to evaluate the effects of ranitidine on intragastric pH and upper gastrointestinal tract bleeding in severe head injury patients. Within 24 hr of the precipitating trauma, 34 adults with Glasgow coma scale scores < or = 10 were randomized to a 6.25 mg/hr ranitidine continuous infusion or placebo for a maximum of 72 hr. Intragastric pH was recorded via an intragastric pH electrode. Patients with hematemesis, hematochezia, bright red blood, or "coffee ground" nasogastric tube aspirates plus a 5% decrease from baseline in hematocrit were considered to have gastrointestinal bleeding. Ranitidine patients maintained a significantly greater mean pH than placebo patients (placebo 2.2, ranitidine 4.1; P < 0.01). All patients had at least two bleeding risk factors at study entry. No ranitidine patients (0/16) developed bleeding compared with five (5/18) placebo patients (P < 0.05). Ranitidine continuous infusion provided consistent intragastric pH control and significant protection from stress-related upper gastrointestinal tract bleeding in a high-risk patient population.