The distribution of nonstenosing, asymptomatic intimal plaques in 12 adult human carotid bifurcations obtained at autopsy was compared with the distribution of flow streamline patterns, flow velocity profiles, and shear stresses in corresponding scale models. The postmortem specimens were fixed while distended to restore normal in vivo length, diameter, and configuration. Angiograms were used to measure branch angles and diameters, and transverse histological sections were studied at five standard sampling levels. Intimal thickness was determined at 15 degrees intervals around the circumference of the vessel sections from contour tracings of images projected onto a digitizing plate. In the models, laser-Doppler anemometry was used to determine flow velocity profiles and shear stresses at levels corresponding to the standard specimen sampling sites under conditions of steady flow at Reynolds numbers of 400, 800, and 1200, and flow patterns were visualized by hydrogen bubble and dye-washout techniques. Intimal thickening was greatest and consistently eccentric in the carotid sinus. With the center of the flow divider as the 0 degree index point, mid-sinus sections showed minimum intimal thickness (0.05 +/- 0.02 mm) within 15 degrees of the index point, while maximum thickness (0.9 +/- 0.1 mm) occurred at 161 +/- 16 degrees, i.e., on the outer wall opposite the flow divider. Where the intima was thinnest, along the inner wall, flow streamlines in the model remain axially aligned and unidirectional, with velocity maxima shifted toward the flow divider apex. Wall shear stress along the inner wall ranged from 31 to 600 dynes/cm2 depending on the Reynolds number. Where the intima was thickest, along the outer wall opposite the flow divider apex, the pattern of flow was complex and included a region of separation and reversal of axial flow as well as the development of counter-rotating helical trajectories. Wall shear stress along the outer wall ranged from 0 to -6 dynes/cm2. Intimal thickening at the common carotid and distal internal carotid levels of section was minimal and was distributed uniformly about the circumference. We conclude that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening. Intimal thickening and atherosclerosis develop largely in regions of relatively low wall shear stress, flow separation, and departure from axially aligned, unidirectional flow. Similar quantitative evaluations of other atherosclerosis-prone locations and corresponding flow profile studies in geometrically accurate models may reveal which of these hemodynamic conditions are most consistently associated with the development of intimal disease.