We have investigated the effect of therapy for Helicobacter pylori gastritis on serum concentrations of pepsinogen I and II in 43 patients. In the 22 patients in whom therapy resulted in dramatic decrease in gastritis scores and in clearance of the bacteria, there was a highly significant (P = 0.0001) fall in mean serum pepsinogen II from 13.3 +/- 0.8 to 7.9 +/- 0.7 micrograms/liter, and a less pronounced fall in pepsinogen I from 89.0 +/- 5.9 to 78.5 +/- 0.4 micrograms/liter (P = 0.01). These changes resulted in a significant (P = 0.01) increase in the pepsinogen I/II ratio. In contrast, nonsignificant declines of 3.5% and 11.6% were observed in mean pepsinogen I and II levels in the 21 patients whose gastritis failed to resolve histologically and whose infection did not clear. These findings suggest that serum pepsinogen levels, especially pepsinogen II, are a new tool that may be found to be clinically useful in evaluation of treatment outcome in patients with H. pylori-associated gastritis.