To evaluate the role of Na(+)-glucose cotransport in fluid absorption across alveolar epithelial walls in isolated rat lungs, we measured the inhibitory effects of amiloride (a Na+ channel blocker) and phlorizin (a Na(+)-glucose cotrasport blocker) on the fluid absorption rate in fluid-filled lungs. Amiloride (10(-5)-10(-4) M) reduced alveolar fluid absorption by 30%. This value was similar to that obtained in the presence of 10(-3) M phlorizin. The coefficient of Na(+)-glucose cotransport was estimated to be 2.5. The strong correlation between Na+ escape and fluid absorption (r = 0.907) was not affected by phlorizin. These findings suggest that the impact of Na(+)-glucose cotransport was similar to that of Na+ transport alone, and that glucose molecules transported by Na(+)-glucose cotransport do not play an important role in alveolar fluid absorption across rat alveolar epithelium.