Lymphoid follicles are a common feature of Helicobacter pylori-associated gastritis. Recently, by using gastric mapping, we demonstrated lymphoid follicles in all of 62 patients with H pylori infection. This study was designed to address (1) the prevalence of lymphoid follicles in routine gastric biopsy specimens, (2) their correlation with chronic active gastritis, and (3) their predictive value with respect to H pylori infection. Slides from 174 patients whose gastric biopsy findings carried a nonneoplastic diagnosis were evaluated for the presence of (1) chronic active gastritis, (2) lymphoid follicles, and (3) H pylori. When either follicles or active gastritis was found, but H pylori could not be identified by the hematoxylin-eosin stain, additional slides were prepared with a newly developed silver-hematoxylin-eosin-alcian blue stain. Active gastritis was present in 153 patients (88%). Helicobacter pylori was identified on hematoxylin-eosin-stained slides in 123 patients and by the modified Steiner stain in 11 additional patients. Thus, 87% of the patients with chronic active gastritis had histologically detectable H pylori infection. One or more lymphoid aggregates were present in 110 patients (82% of patients with H pylori and 72% of those with chronic active gastritis). Of these, 101 (92%) had H pylori infection. In six of the nine H pylori-negative patients with lymphoid aggregates, biopsy specimens were taken from the edges of an ulcer. In summary, except when biopsy specimens are obtained from the immediate vicinity of a gastric ulcer, lymphoid aggregates in a gastric biopsy specimen are virtually always associated with chronic active gastritis and provide a useful marker for H pylori infection.