We assessed the heterogeneity of regional pulmonary blood flow (PBFr), using radioactive microspheres in five unanesthetized dogs standing at rest (Rest), standing at a 45 degrees upward tilt (Tilt), and during moderate treadmill exercise (Exer). The excised lungs were cut into 1-cm3 pieces along transverse, horizontal, and longitudinal planes. Mean PBFr increased from 23.3 ml.min-1.g-1 at Rest to 57.4 ml.min-1.g-1 during Exer, but the relative dispersions were not statistically different between states (47.3-51.9%). A small but significant gravity-dependent gradient in PBFr of < or = 4.7%/cm (r2 < or = 0.118) as well as a PBFr decreasing radial gradient from the lung midpoint of < or = 7.2%/cm (r2 < or = 0.108) were present in all states. PBFr at Rest was highly correlated with those at Tilt (r2 = 0.773) and Exer (r2 = 0.888), and a variable PBFr gradient of < or = 2.5%/cm from base to apex was observed. Fractal dimensions calculated using relative dispersion as a function of aggregated sample size were not significantly different between states and were 1.132 (r2 = 0.987) at Rest, 1.121 (r2 = 0.973) at Tilt, and 1.149 (r2 = 0.986) during Exer. Thus, gravity and centripetal gradients consistently accounted for a maximal difference of only about twofold in PBFr and < 11% of overall PBFr heterogeneity in 1-cm3 samples. Recursive anatomic branching of pulmonary arteries and local mechanical factors apparently account for most of the blood flow heterogeneity in small pieces of lung.