The effect of diazepam on the lower esophageal sphincter (LES) pressure was studied in a controlled randomized double-blind protocol. Twenty-five patients received intravenous saline, diazepam 5 mg. and diazepam 10 mg. on different days. Diazepam 5 mg. and diazepam 10 mg. caused a mean peak reduction in LES pressure of 18.9 and 37.8% respectively. The peak reduction in LES pressure was dose-related and lasted approximately seven minutes. Awareness of diazepam's ability to significantly lower LES pressure is needed to avoid the possibility of falsely diagnosing reflux by endoscopy. The mechanism whereby diazepam lowers LES pressure is not known, however, diazepam may be acting as a smooth muscle relaxant since myogenic influences have been implicated in the genesis of LES pressure.