Although the histopathologic patterns associated with Helicobacter pylori infection have been described, details of the interaction between bacteria, epithelial cells, and inflammatory cells remain elusive. One of the limiting factors has been the lack of a staining technique that allows the simultaneous visualization of H pylori and tissue morphology. By combining three commonly available stains (Steiner, hematoxylin-eosin, and alcian blue at pH 2.5) into a single procedure we have developed a stain that permits the optimal detection of H pylori in tissue sections while simultaneously allowing the histopathologic evaluation of all salient characteristics of the gastric mucosa. This procedure is inexpensive, as easy to perform as any silver stain, and provides consistent results. This stain is as sensitive as the Warthin-Starry stain for the detection of H pylori and significantly more sensitive than hematoxylin-eosin alone (> 99% v 85% when compared with the hematoxylin-eosin stain in a series of 332 positive biopsy specimens; > 99% v 61% in 49 biopsy specimens with rare bacteria). This stain is particularly useful for the visualization of small numbers of bacteria, such as in the evaluation of posttreatment gastric biopsy specimens, in specimens with abundant mucus or debris, and in specimens from the corpus, where H pylori usually does not elicit strong inflammatory responses and, therefore, pathologists' index of suspicion tends to be low.