The aim of this prospective, placebo-controlled study was to assess if unilaterally inhaled nitric oxide 20 ppm could treat hypoxaemia during one-lung ventilation. Sixty patients undergoing pulmonary resection using a lateral thoracotomy were allocated randomly to a control or nitric oxide group (NO group). During one-lung ventilation in the lateral decubitus position, the lungs were ventilated mechanically with 90% oxygen--10% nitrogen. After randomization, if PaO2 decreased to less than 9.3 kPa during one-lung ventilation, nitric oxide 20 ppm or nitrogen was added to the inspired gas. The criterion for treatment efficacy was an increase in PaO2 to greater than 9.3 kPa after gas administration. Eight patients in the control group and eight in group NO experienced hypoxaemia during one-lung ventilation. PaO2 was not significantly different in the two groups at the time of gas administration (control group mean 8.0 (SD 0.6) kPa; NO group 8.5 (0.5) kPa). The efficacy criterion was reached in two of eight patients in the control and NO groups. The results of this study showed that inhaled nitric oxide 20 ppm, administered in the dependent lung, was not superior to nitrogen in the treatment of hypoxaemia during one-lung ventilation. Nitric oxide should not be recommended as an alternative to conventional management of hypoxaemia in this condition.