The rabbit represents a popular animal model for basic science research, but projects requiring anesthesia and endotracheal intubation represent a technical challenge because of the difficulty in accessing the animal's airway and sensitivity to common anesthetic agents. We hypothesized that transoral intubation under direct visualization with guidewire assistance would improve airway access success and reduce perioperative mortality in the rabbit. Of the 39 New Zealand White rabbits that had passive inhalation anesthesia and were intubated using wire-guided assistance under direct laryngeal visualization, 33 were intubated using a flexible wire after the rigid guide had resulted in airway injury in three of the first six rabbits. Animals were then maintained under general anesthesia during a 4- to 5-h procedure. At the completion of the procedure, animals were recovered from anesthesia and extubated. All 39 animals were successfully intubated, mostly on the first attempt. There were two animal deaths, both in the first six animals; one death was a direct result of laryngeal injury from the rigid wire guide initially used. One additional animal in the first six had pulmonary difficulty after an airway injury but recovered and was successfully used in the experiment. Two animals developed gastric distention during anesthesia, which was alleviated with placement of an orogastric tube without adverse sequelae. No animals developed problems with oxygenation during the experiment, but over half (52.8%) had end-tidal CO2 (ETCO2) above 45 mmHg at least once during the surgery, and 13 rabbits were above this level for longer than 1 h. An average of 18 min elapsed between withdrawal of anesthesia and the time when spontaneous respirations and chewing movements returned. Animals then could be safely extubated. There was no correlation between high perioperative ETCO2 and time to recovery from anesthesia (P = 0.18, r = 0.23).