Glutathione S-transferases (GSTs) form a family of enzymes, which play an important role in the prevention of cancer by detoxifying numerous potentially carcinogenic compounds. GSTs catalyze the conjugation of glutathione to such harmful molecules, and enable their secretion. Human GSTs can be divided into five main classes. The theta class of isoenzymes was only recently identified and limited (immunohistochemical) data on these enzymes are available. In the present study, paraffin-embedded sections of different gastrointestinal tissues were analyzed immunohistochemically for GSTalpha, GSTP1-1 and GSTT1-1 expression using specific antibodies. GSTalpha, GSTP1-1 and GSTT1-1 were highly expressed in all gastrointestinal tissues examined, with a unique cellular distribution. GSTT1-1 is the first GST isoenzyme demonstrated in duodenal Paneth cells and glands of Brunner. The common expression of GSTalpha, GSTT1-1 and GSTP1-1 in many cell types along the human gastrointestinal tract suggests an important role in the protection against carcinogens and other xenobiotics.