The effect of Helicobacfer pylori protein on cAMP and prostaglandin (PGE,) production was studied in incubates of human gastric fundic mucosa.At 24 hours, specimens incubated in the control fluid had a median cAMP value of 81 pmol/mg protein, compared to 28 pmol/mg ( P < 0.05) when incubated in H. pylori protein, 155 pmol/kg ( P < 0.006) in histamine, and 23 pmol/kg ( P < 0.05) in histamine plus H. pylori protein.A similar trend was observed at 48 hours. Although H. pylori protein had no direct effect on mucosal PGE,, it intensified the inhibitory effect of indomethacin and prevented the stimulatory effect of histamine on both PGE, and cAMP production. Given the role of cAMP in various physiological responses, these results suggest that H. pylori protein might alter those functional aspects of the human gastric mucosa which rely on cAMP as a second