The fate of inhaled NO2 was studied with isolated perfused rat lungs. The isolated lungs were exposed to 5 ppm NO2 for 90 min at a ventilation rate of 45 ml/min. The NO2 exposure had no adverse effects on the lungs as judged from their weights, glucose uptake, or lactate production compared to control lungs. Isolated lungs absorbed 36% of ventilated NO2, which was detected in perfusate and lung tissue as NO2 but not NO3. The NO2 concentration in perfusate increased linearly with time, and after 90 min of ventilation with NO2 and perfusion with erythrocyte-free medium the NO2 accumulation was 6.36 + or - 0.39 ug. If perfusate contained 10% erythrocytes, the ventilated NO2 product was mostly NO3 in perfusate but NO2 in lung tissue. Protein solutions absorbed NO2 more effectively than simple salt solutions, but they all yielded mainly NO2 unless erythrocytes were present, when the product was mostly NO3. The results indicate that absorbed NO2 in the lung is converted predominantly to NO2, but after its diffusion into the vascular space it is oxidized to NO3 by interactions with erythrocytes.