OBJECTIVE We compared histologic sections with in vitro sonographic images for 40 resected gallbladder specimens to correlate the histopathologic processes with the sonographic appearance of the gallbladder wall. METHODS In vitro sonographic images and histologic specimens were obtained by use of a specimen container with a micropositioner. An 8.5-MHz transducer and a scalpel were attached to the micropositioner to obtain the sonographic image and the histologic section. The sonographic images were analyzed for wall thickness and the number and echo texture of the visualized layers and then were correlated with the histologic sections. Each histologic specimen was interpreted as being normal or showing mild, chronic, acute, or gangrenous cholecystitis. RESULTS One to four sonographic layers were observed in the gallbladder wall specimens. The number of wall layers was fairly evenly distributed among the different types of gallbladder wall inflammation. One to three sonographic layers were observed for most of the different types. In nearly all instances, the findings were attributable to either similar pathologic processes in two or more histologic layers or different pathologic processes in a single histologic layer. The gallbladder wall measured less than or equal to 3 mm in 89% of gallbladders with normal or mild inflammation, greater than 3-6 mm in 71% of cases of chronic cholecystitis, greater than 3 mm in 83% of cases of acute cholecystitis, and greater than 6 mm in 50% of cases of gangrenous cholecystitis. CONCLUSIONS The sonographic layers in the inflamed gallbladder wall are determined by the pathologic changes present rather than by the normal histologic boundaries. However, because of the overlap of pathologic changes, we cannot predict the type of gallbladder wall pathology on the basis of the sonographic appearance. We found a trend toward gallbladder wall thickening for severely inflamed gallbladder walls.