AIMS: To investigate interleukin (IL)-12 (p40) and IL-10 mRNA expression levels in the gastric mucosa in relation to H pylori cag status, peptic ulceration, and histopathology. METHODS: In 81 dyspeptic patients, antral and corpus biopsies were taken for reverse transcriptase polymerase chain reaction (RT-PCR) and histology. G3PDH (control) and IL-10 and IL-12 were coamplified in a duplex PCR and the ratios of cytokines to G3PDH were determined. Bacterial ureA and cagA status was determined by RT-PCR. RESULTS: IL-10 mRNA expression in both the antral and corpus mucosa was greater (p < 0.01) in cagA positive infection than in H pylori negative patients with histologically normal mucosa. No increase in IL-10 mRNA expression was observed in cagA negative infection. Both in the antral and corpus mucosa, IL-12 mRNA expression was greater (p < 0.05) in cagA positive than in cagA negative infection and uninfected patients with normal gastric mucosa. In cagA positive infection, there was a correlation between IL-10 and IL-12 mRNA expression in both the antral mucosa (r = 0.515, p < 0.01) and the corpus mucosa (r = 0.6, p < 0.005). IL-12 mRNA expression in the antral mucosa was significantly more frequent in H pylori positive patients with duodenal ulcer than in those with gastric ulcer or nonulcer dyspepsia. No difference was observed in IL-10 mRNA expression in relation to endoscopic diagnosis. CONCLUSIONS: CagA positive H pylori infection is associated with increased IL-10 and IL-12 mRNA expression. The increased expression of IL-12 mRNA in the majority of patients with duodenal ulcer suggests that Th1 responses may predominate and play a role in the pathogenesis of duodenal ulceration.