Inhaled nitric oxide (iNO) therapy is an effective treatment of pulmonary hypertension following left ventricular assist device (LVAD) implantation. As iNO may also modulate circulating endothelin-1 (ET-1) and big endothelin following LVAD implantation, we investigated the effects of iNO on ET-1 and big endothelin plasma concentration gradients. In order to assist weaning from cardiopulmonary bypass, iNO was administered to 15 consecutive patients with secondary pulmonary hypertension following implantation of a LVAD. Central venous, pulmonary arterial and arterial ET-1 and big endothelin plasma levels were measured preoperatively, on cardiopulmonary bypass prior to iNO administration, 12, 24 and 48 hours postoperatively, and 72 hours after weaning from iNO. The ET-1 gradients between central venous and pulmonary arterial plasma levels decreased significantly with time, and there was a trend for lower arterial-pulmonary arterial plasma concentration gradients. Big endothelin plasma concentration gradients were not altered significantly. The decrease in ET-1 plasma concentration gradients during and after iNO administration may reflect a restoration of the physiologic balance between the different vascular beds. This provides further evidence that intermittent iNO therapy may modulate ET-1 after LVAD implantation.