The measurement of nitric oxide (NO) in expired gas is being increasingly reported in disease states such as sepsis, heart failure, and asthma. However, the effects of changes in ventilatory and cardiac parameters on expired NO are not known. Therefore, we assessed the effects of changes in minute ventilation (VE), ventilatory pattern, and cardiac output on expired gas NO levels in five anesthetized, intubated pigs. The animals were mechanically ventilated at three settings for each of respiratory rate (12 to 14, 16 to 18, and 22 to 24/min) and tidal volume (10, 15, and 20 mL/kg) applied in random sequence, yielding nine ventilatory patterns and a range of VE (3.7±0.1 to 13.2±0.8 L/min). When VE was increased, expired NO concentration declined slightly (r=−0.40, p<0.01), but the rate of excretion of NO in expired gas increased significantly (r=0.60, p<0.01). In contrast, when cardiac output was increased progressively from 3.6±0.1 to 4.7±0.3 and 5.8±0.4 L/min (p<0.01) by volume loading during constant eucapneic ventilation, there was no change in expired NO. Changes in VE over a physiologic range significantly affect the measurement of NO in expired gas, whereas short-term changes in cardiac output do not. To facilitate comparison between studies, we suggest that the measurement of expired NO should be reported in conjunction with data on VE.