Carditis has become the subject of much study and discussion, although its etiology is still controversial. We wished to study the prevalence and possible pathogenetic mechanisms of carditis in a well-defined group of patients. In 664 patients biopsies were taken distal to the squamocolumnar junction (SCJ) and from the endoscopically defined cardia (2 cm below proximal margin of gastric folds). Specimens were stained with hematoxylin and eosin, Alcian blue, and modified Giemsa. Type of mucosa, inflammatory and metaplastic changes, and presence of Helicobacter pylori (Hp) were graded. Most of the patients had a normal appearing SCJ on endoscopy; 19.3% had short columnar segments (1-3 cm). In the first group cardiac/mixed mucosa was found in 71.9% of SCJ biopsies, and carditis (90.6%) was associated with Hp. In the second group, cardiac/mixed mucosa was present in 80.5%. There was a trend for an association between carditis (87.4%) and reflux esophagitis and hiatal hernia. Biopsies from the endoscopically defined cardia rarely contained cardiac/mixed mucosa (12.6%). These findings suggest two etiologies for carditis. In a normal-appearing SCJ carditis is associated with Hp, whereas in an irregular SCJ with short columnar segments/tongues carditis is associated with features of gastroesophageal reflux.