&NA;The purpose of this study was to determine whether the behavior of sonicated albumin microbubbles accurately mimics red blood cell flow in the microcirculation and is thus consistent with their use as in vivo tracers of red blood cell flow during myocardial contrast echocardiography. Accordingly, microbubbles prepared from fluorescein‐conjugated albumin and fluorescently labeled red blood cells were injected intravascularly in eight golden hamsters. Their intravascular distribution, velocities, arteriolar‐to‐venular transit times, and flux ratios at branch points were determined in the microcirculation of the cheek pouch. Albumin microbubbles (mean diameter, 4.9±3.6 &mgr;m) and red blood cells displayed a similar frequency of distribution across the arteriolar lumen (33% in the central 20% of the arterioles), and their arteriolar velocities were also similar (2.5±0.7 mm/sec and 2.3±0.7 mm/sec,p=NS). The mean velocities of microbubbles correlated well with those of red blood cells at baseline and after adenosine application (r=0.97 andr=0.89, respectively), as did the calculated maximum velocity (r=0.98 andr=0.80, baseline and adenosine, respectively). The velocity profiles across the lumen of the vessels for albumin microbubbles and red blood cells were similar at baseline and after adenosine‐induced velocity changes. The flux ratios at branch points also correlated well (r=0.92,p<0.001). Arteriolar‐to‐venular transit times of albumin microbubbles were similar to those of red blood cells in vessels ranging in size from 22 &mgr;m to 45 &mgr;m. We conclude that the behavior of albumin microbubbles in the microcirculation mimics that of red blood cells and supports their use as intravascular tracers of red blood cell flow during myocardial contrast echocardiography. (Circulation Research1989;65:458‐467)