Tonsillar tissue is a component of mucosa-associated lymphoid tissue (MALT), which has evolved to protect vulnerable mucosal surfaces. Helicobacter pylori, implicated as an aetiological factor in duodenal ulcers and gastritis, induces the appearance of lymphoid aggregates (MALT) in the stomach. This organism is cytotoxic via a nitric oxide synthase cascade. The possibility that tonsillar tissue processes Helicobacter pylori or that Helicobacter pylori can colonize the palatine tonsils is explored. The study design was that of a prospective study. We determined if Helicobacter pylori (i) forms part of the normal microenvironment of the tonsil, (ii) plays a role in the pathogenesis of tonsillitis and (iii) is associated with increased expression of inducible nitric oxide synthase (iNOS) in macrophages of the tonsil. Serology for Helicobacter pylori was performed on 50 patients undergoing tonsillectomy. Tonsillar specimens were monitored for urease activity by CLO test (a sealed plastic slide holding an agar gel, which contains urea and detects the urease enzyme of Helicobacter pylori), and immunocytochemically probed for Helicobacter pylori and iNOS expression. The mean age of this patient group was 17.2 years (3-36 years). Fourteen (28%) were sero-positive for Helicobacter pylori but no evidence of this pathogen was found in any tonsillar specimen. The number of macrophages staining for iNOS, per field, under a magnification of x40, was increased in sero-positive patients (13.3 +/- 1.3 versus 9.9 +/- 0.7; P = 0.01). Helicobacter pylori does not appear to colonize the tonsil. We believe that Helicobacter pylori primes the tonsils by inducing macrophage iNOS expression. The higher expression in sero-positive patients is a reflection of a pro-inflammatory reaction to Helicobacter pylori that is both local and systemic.