Because neonates are vulnerable to spontaneous nasal obstruction, this study was designed to evaluate the ventilatory consequences of obstructing a single nasal passage in preterm infants. We employed a nasal pneumotachograph that separately quantified airflow between the two nasal passages and permitted unilateral nasal mask occlusions. Changes in minute ventilation (V̇(I)) and total (R(T)) and inspiratory pulmonary resistance (R(I)) were measured in response to 30-s unilateral occlusions during quiet and active sleep in 11 subjects. Unilateral nasal obstruction caused V̇(I) to fall significantly in both sleep states, because of a fall in both tidal volume and respiratory rate, without alteration in transcutaneous blood gases. R(T) and R(I) increased by 27 and 24 cmH2O·l-1·s, respectively, during unilateral nasal occlusion; this increase was greater than would be expected solely from elimination of one nasal passage. In 7 of the 11 infants a single dominant side could be identified as contributing 56-67% to tidal volume. The effect of occlusion on V̇(I), R(T), or R(I) did not differ whether the dominant or nondominant side was occluded. We conclude that unilateral nasal mask occlusion increases R(T) and R(I) and decreases V̇(I) in preterm infants. The larger than expected increase in resistance suggests that unilateral nasal loading predisposes to narrowing of the extrathoracic airway, and this may explain the comparable ventilatory responses to occluding the dominant and nondominant nasal passage.