Hypoxemia during esophagogastroduodenoscopy (EGD), or panendoscopy has been generally attributed to sedation. We studied 49 patients ranging in age from 17 to 71 years with normal or nearly normal lung function undergoing EGD to determine the effects of sedation and the effects of the endoscope on arterial oxygen saturation (SaO2). All patients received intravenous diazepam and 41 also received meperidine. EGD was delayed 10.7 ± 7.5 min after intravenous diazepam administration in the 42 group 1 patients. Seven patients underwent EGD within 2 min of receiving intravenous diazepam (group 2). Ventilation decreased after diazepam, recovered, then decreased immediately after endoscope insertion in the group 1 patients. Periods of hypopnea, up to 39 s long, were observed during EGD. The average decrease in SaO2was 4.0% after diazepam (p < 0.0001). SaO2returned to the pre-EGD level, then decreased 2.4% during EGD (p < 0.0005). Maximum SaO2decrease occurred 27 ± 6 s after insertion of the endoscope then rapidly recovered. There was a linear correlation between the duration of hypopnea and maximum SaO2decrease (r = 0.84, p < 0.001). All group 2 patients experienced a period of hypopnea (13.3 ± 9.6 s) and SaO2declined 9.0%. The SaO2decline was significantly greater in the group 2 subjects (p < 0.0001). Our results confirm previous findings that intravenous sedation causes hypoventilation and hypoxemia. Moreover, hypoventilation and further arterial oxygen desaturation are caused by either the mechanical effect of the endoscope or a reflex stimulated by it.