Despite the heterogeneous distribution of regional pulmonary perfusion over space, local perfusion remains stable over short time periods (20-100 min). The purpose of this study was to determine whether the spatial distribution of pulmonary perfusion remains stable over longer time periods (1-5 days). Regional blood flow was measured each day for 5 days in five awake standing dogs. Fluorescent microspheres of different colors were injected into a limb vein over 30 s on each day. After the last microsphere injection, the dogs were killed, and lungs were flushed free of blood, excised, dried at total lung capacity, and diced into similar to 2-cm(3) pieces (n = 1,296-1,487 per dog). Relative blood flow to each piece on each day was determined by extracting the fluorescent dyes and determining the concentrations of each color. We established that blood flow is spatially heterogeneous with a coefficient of variation of 29.5 +/- 2%. Blood flow to each piece is highly correlated with flow to the same piece on all days (r = 0.930 +/- 0.006). The temporal heterogeneity of regional perfusion as measured by the coefficient of variation is 6.9 +/- 0.7% over the 5 days and is nonrandom. The magnitude of spatial and temporal variation is significantly less than previously reported in a study in which anesthetized and mechanically ventilated dogs were used. We conclude that spatial distribution of pulmonary blood flow remains stable over days and we speculate that in the normal awake dog regional perfusion is determined primarily by a fixed structure such as the geometry of the pulmonary vascular tree rather than by local vasoactive regulators. Anesthesia and/or mechanical ventilation may increase the temporal variability in regional perfusion.