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A recent study suggested that cimetidine prolongs the duration of action of succinylcholine (SCh). We examined this reported interaction, and investigated whether it is the result of inhibition of plasma cholinesterase (PChE). We also studied the effect of ranitidine on the duration of action of succinylcholine. Thirty patients were randomly assigned to three groups to receive oral cimetidine 300 mg or ranitidine 150 mg or no H2-antagonist the night before surgery and again 1-2 hours prior to induction of anesthesia. Succinylcholine (1.5 mg/kg i.v.) was given to facilitate tracheal intubation after induction of anesthesia; neuromuscular function was monitored by evoked compound electromyogram. Pretreatment blood samples were analyzed for PChE activity. PChE activity and levels of appropriate H2-antagonists were measured in preinduction blood samples. No significant effect of either cimetidine or ranitidine on the duration of action of SCh or PChE activity was demonstrated. We conclude that H2-antagonists administered preoperatively do not prolong the duration of action of succinylcholine or alter PChE activity.