Both regional ventilation and regional perfusion demonstrate progressive increases in heterogeneity as the resolution of measurement is improved. Because the efficiency of pulmonary gas exchange is dependent on the match between local ventilation and local perfusion, the correlation between these two parameters was examined over a range of scale. We marked regional ventilation and perfusion in three anesthetized pigs with aerosolized 1 mum fluorescent microspheres (FMS) and injected 15 mum FMS. The lungs were dried inflated, cut into similar to2 cm(3) cubes, and regional ventilation and blood flow were calculated from measurements of the fluorescence signals extracted from each piece. Adjacent pieces were clustered into successively larger aggregate volumes, and the averages of ventilation and of perfusion were calculated for each cluster size. While the coefficient of variation for both ventilation and perfusion increased predictably as the cluster size decreased, the correlation between ventilation and perfusion within clusters remained high, averaging between 0.82 and 0.92 among animals. Thus, while both ventilation and perfusion heterogeneity increase as the resolution of measurement improves, the strong correlation between these two parameters in a normal prone lung is nearly sample size invariant. This finding explains the observed efficiency of normal gas exchange in the face of the substantial degree of ventilation and perfusion heterogeneity observed in the normal lung with high-resolution measurement.