This study compares sonographic and histologic findings within defined spatial regions in carotid artery plaque, using computer generated three-dimensional reconstructions. Twenty-four patients (14 asymptomatic, 10 symptomatic) with angiographically documented 70% to 99% carotid artery stenosis were examined with ultrasonic B-mode imaging prior to endarterectomy. Using a standardized protocol for instrument set-up and scanning technique, echolucent regions in the plaque were identified. After endarterectomy, each plaque was sectioned at 0.5 to 1.0 millimeter increments throughout its length. Sites containing intraplaque hemorrhage, cholesterol clefts, foam cells, necrotic cores, dense calcification and speckled calcification were identified. These areas were outlined on a template, digitized and imported into a computer program that created three-dimensional reconstructions of the histologic findings. Each carotid plaque was divided into quadrants for analysis: (1) lateral wall proximal to the common carotid bifurcation (flow divider); (2) medial wall proximal to the flow divider; (3) lateral wall distal to the flow divider; and (4) medial wall distal to the flow divider. The odds of finding intraplaque hemorrhage, foam cells, necrotic cores and speckled calcification were significantly higher in quadrants with an echolucent region identified by ultrasonography (odds ratio (95% confidence interval) for intraplaque hemorrhage = 3.5 (1.4-8.6); foam cells = 4.0 (1.6-9.9); necrotic cores = 3.2 (1.2-8.4); speckled calcification = 4.0 (1.6-9.8). This preliminary analysis demonstrates the potential of these newly developed techniques for comparing ultrasonic imaging to histology.