Gastric cancer is often associated with p53 over-expression and Helicobacter pylori (HP) infection. In this study we have investigated the production of the p53 protein and mutation of its gene in precancerous gastric lesions with HP infection. For this purpose 130 patients who underwent endoscopy for dyspepsia were enrolled in the study. To assess p53 production and mutation of the p53 gene we employed an immunoluminometric assay and polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analysis, respectively. Histologically, 52 of the 130 enrolled patients showed intestinal metaplasia type I (IM) (90.4% of these were also HP positive), 47 had HP-related gastritis and 31 were normal. p53 cytosol levels were significantly higher in patients with IM or HP-related gastritis than in normal patients (p = 0.0137 and p = 0.0411, respectively). All DNAs extracted from gastric mucosa samples with higher p53 values and examined for p53 mutations by PCR-SSCP analysis were characterized by a normal run. Our data indicate, that irreversible genetic changes in the p53 protein has not yet occurred in morphologically non-neoplastic gastric mucosa with IM and HP-related chronic gastritis. In conclusion, the increase in p53 cytosolic levels found in our study is due to an increased production of the wild-type protein probably related to an inflammatory response induced by HP infection.