Studies have suggested that inducing mild hypothermia improves neurologic outcomes after traumatic brain injury, major stroke, cardiac arrest, or exertional heat illness. While infusion of cold normal saline is a simple and inexpensive method for reducing core temperature, human cold-defense mechanisms potentially make this route stressful or ineffective. We hypothesized that intravenous administration of diazepam during a rapid infusion of 30 mL.kg-1 of cold (4 degrees C) 0.9% saline to healthy subjects would be more comfortable and reduce core body temperature more than the administration of cold saline alone. Fifteen subjects received rapidly infused cold (4 degrees C) 0.9% saline. Subjects were randomly assigned to receive, intravenously, 20 mg diazepam (HIGH), 10 mg diazepam (LOW), or placebo (CON). Main outcomes were core temperature, skin temperature, and oxygen consumption. Data for the main outcomes were analyzed with generalized estimating equations to identify differences in group, time, or a group x time interaction. Core temperature decreased in all groups (CON, 1.0 +/- 0.2 degrees C; LOW, 1.4 +/- 0.2 degrees C; HIGH, 1.5 +/- 0.2 degrees C), while skin temperature was unchanged. Mean (95% CI) oxygen consumption was 315.3 (253.8, 376.9) mL.kg-1.min-1 in the CON group, 317.9 (275.5, 360.3) in the LOW group, and 226.1 (216.4, 235.9) in the HIGH group. Significant time and group x time interaction was observed for core temperature and oxygen consumption (p < 0.001). Administration of high-dose diazepam resulted in decreased oxygen consumption during cold saline infusion, suggesting that 20 mg of intravenous diazepam may reduce the shivering threshold without compromising respiratory or cardiovascular function.