Cholecystokinin (CCK) release after a standard test meal is decreased in coeliac patients. The aim of the study was to determine the origin of the CCK deficiency and the relationship between the distinctive types of mucosal lesions observed in coeliac disease and the number of duodenal CCK cells and their peptide and mRNA content. Duodenal biopsies were obtained in ten controls and nineteen coeliac patients [seven with atrophic mucosa, six with increased numbers of intraepithelial lymphocytes (IELs) and six with fully normalized mucosa]. Immunocytochemistry was performed with a CCK C-terminal-specific polyclonal antiserum. The CCK cells were counted and related to the epithelial area using a semi-automated image analyser. CCK content in mucosal extracts was determined by radioimmunoassay. mRNA was measured with a semi-quantitative reverse transcriptase-PCR method using specific CCK and ribosomal protein L19 (RPL19) primers. CCK tissue concentration and CCK mRNA were significantly reduced in patients with atrophic mucosa [12.2 (range 6.9-17.5) pmol/g; CCK/RPL19 ratio 0.64 (0.30-0.99)] compared with patients with normal mucosa [40.5 (30.4-50.7) pmol/g; CCK/RPL19 ratio 1.40 (0.41-2.40)] or controls [42.7 (18.2-67.2) pmol/g; CCK/RPL19 ratio 1.35 (1.09-1.62)]. A similar decrease was observed in patients with an excess of IELs, 13.9 (3.8-31.8) pmol/g and 0.86 (0.57-1.15) pmol/g respectively. The number of CCK cells was, however, similar in all groups. Duodenal CCK concentration and mRNA are decreased not only in the mucosa presenting atrophic changes but also when disease activity is limited to infiltration by IELs. Reduced expression of the CCK gene could therefore be related to suppressive factors induced by the inflammatory infiltrate.