OBJECTIVES: Injection of water into the pharynx induces contraction of the upper esophageal sphincter (UES), triggers the pharyngo-UES contractile reflex (PUCR), and at a higher volume, triggers an irrepressible swallow, the reflexive pharyngeal swallow (RPS). These aerodigestive reflexes have been proposed to reduce the risks of aspiration. Alcohol ingestion can predispose to aspiration and previous studies have shown that cigarette smoking can adversely affect these reflexes. It is not known whether this is a local effect of smoking on the pharynx or a systemic effect of nicotine. The aim of this study was to elucidate the effect of systemic alcohol and nicotine on PUCR and RPS. METHODS: Ten healthy non-smoking subjects (8 men, 2 women; mean age: 32 +/- 3 s.d. years) and 10 healthy chronic smokers (7 men, 3 women; 34 +/- 8 years) with no history of alcohol abuse were studied. Using previously described techniques, the above reflexes were elicited by rapid and slow water injections into the pharynx, before and after an intravenous injection of 5% alcohol (breath alcohol level of 0.1%), before and after smoking, and before and after a nicotine patch was applied. Blood nicotine levels were measured. RESULTS: During rapid and slow water injections, alcohol significantly increased the threshold volume (ml) to trigger PUCR and RPS (rapid: PUCR: baseline 0.2 +/- 0.05, alcohol 0.4 +/- 0.09; P=0.022; RPS: baseline 0.5 +/- 0.17, alcohol 0.8 +/- 0.19; P=0.01, slow: PUCR: baseline 0.2 +/- 0.03, alcohol 0.4 +/- 0.08; P=0.012; RPS: baseline 3.0 +/- 0.3, alcohol 4.6 +/- 0.5; P=0.028). During rapid water injections, acute smoking increased the threshold volume to trigger PUCR and RPS ( PUCR: baseline 0.4 +/- 0.06, smoking 0.67 +/- 0.09; P=0.03; RPS: baseline 0.7 +/- 0.03, smoking 1.1 +/- 0.1; P=0.001). No similar increases were noted after a nicotine patch was applied. CONCLUSIONS: Acute systemic alcohol exposure inhibits the elicitation PUCR and RPS. Unlike cigarette smoking, systemic nicotine does not alter the elicitation of these reflexes.