Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function.