In rabbits which were initially conscious or lightly anaesthetized with pentobarbitone, ketamine respectively increased or did not change arterial pressure, whereas in mechanically ventilated animals there was prolonged depression of both pressure and pregangkioinic sympathetic activity. Although respiratory rate slowed during spontaneous ventilation, blood-gas changes were not responsible for these differences. Following bilateral division of the carotid sinus and aortic nerves, a depressor response to ketamine occurred during spontaneous respiration. When respiratory rate was slowed coincidentally with ketamine injection during mechanical ventilation, the circulatory responses were similar to those during spontaneous respiration; this did not occur after carotid and aortic denervation. These variations in the circulatory effects of ketamine, according to respiratory pattern and background anaesthesia, are discussed.