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Previous investigations in laboratory animals have documented the ability of the volatile anesthetics to prolong the QT interval and the QT interval corrected for level of heart rate, QTc. The purpose of the present investigation was to evaluate the direct electrocardiographic and hemodynamic effects of enflurane, isoflurane, and halothane in healthy, unpremedicated patients using an inhalation induction to avoid the confounding effects of other anesthetic agents. Experiments were conducted in 22 adult male patients, (ASA physical status I or II) divided into three groups given either enflurane (n = 6), isoflurane (n = 8), or halothane (n = 8) anesthesia. Twenty-four-hour preoperative, preinduction, and postinduction hemodynamic and electrocardiographic measurements were obtained. Anesthetic blood concentrations, levels of plasma electrolytes, and arterial blood gas tensions were also quantitated. Halothane administration (0.81 ± 0.06 mM) did not significantly alter the PR interval or QRS duration but significantly increased the QT (0.38 ± 0.01 to 0.45 ± 0.01 s) and QTc intervals (0.39 ± 0.01 to 0.44 ± 0.02 s). Isoflurane anesthesia (1.04 ± 0.11 mM) did not significantly change QRS duration or PR and QT intervals but significantly prolonged the QTc interval (0.42 ± 0.01 to 0.47 ± 0.14 s). Similarly, enflurane anesthesia (2.16 ± 0.13 mM) significantly prolonged the QTc (0.40 ± 0.01 to 0.46 ± 0.14 s) without change in QRS duration or PR and QT intervals. Plasma electrolyte levels and arterial gas tensions remained within normal limits in all patients. All patients maintained a normal sinus rhythm during the study despite prolongation of the QTc induced by the volatile anesthetics. These results extend previous observations in experimental animals to humans and suggest that ventricular repolarization is directly altered by the volatile anesthetics. Despite the absence of cardiac arrhythmias in this study, prolongation of the QTc interval by volatile inhalation anesthetics suggests that caution should be used during administration of volatile anesthetics to patients with congenital, acquired, or pharmacologically induced prolongation of the QTc.