Abstract We investigated the influence of cardiac innervation on atrial natriuretic factor (ANF) release in baboons. For this purpose, plasma ANF levels were measured in control conditions and in response to head-down (−45°) and head-up tilt (+45°) in six anesthetized baboons before and after complete cardiac denervation obtained by orthotopic autotransplantation of the heart. Cardiac denervation did not modify baseline plasma ANF levels (60.4 ± 17 pg/ml before and 63.1 ± 16 pg/ml after heart autotransplantation). In contrast the significant ANF responses to changes in central venous pressure (CVP) induced by postural maneuvers (−45°, + 16.2 ± 4 pg/ml; +45°, −18.5 ± 4 pg/ml) were markedly alterated after cardiac denervation (−45°, + 5.8 ± 2 pg/ml; +45°, −7.6 ± 1 pg/ml). The changes in CVP and systemic blood pressure evoked by the postural challenges were comparable before and after cardiac denervation. These results demonstrate that cardiac nerves play a role in the control of ANF release.