We determined the effect of postgastrectomy gastritis on serum pepsinogen I and pepsinogen II concentrations in 108 subjects with subtotal gastric resection. Eleven had normal remnant mucosa, 22 had superficial gastritis, and 75 had atrophic gastritis. In the subjects with superficial gastritis, serum pepsinogen I and II concentrations were significantly higher than in those with normal remnant mucosa, but the ratio of pepsinogen I to II did not differ from normal. In atrophic gastritis, serum pepsinogen I concentrations fell with increasing severity of mucosal damage, but pepsinogen II was persistently raised. Consequently, the ratio of pepsinogen I to II in subjects with atrophic gastritis was significantly lower than in those with superficial gastritis or normal remnant mucosa. Discriminant function analysis revealed that the ratio of pepsinogen I to II, in combination with the absolute level of pepsinogen II, had a sensitivity of 80%, a specificity of 73%, and a positive predictive value of 87% for atrophic gastritis in this population. We propose that the parallel increase in serum pepsinogen I and II concentrations in postgastrectomy superficial gastritis is because of an increased rate of endocrine release of both zymogens from the fundic glands, and that the dichotomy in pepsinogen I and II concentrations in postgastrectomy atrophic gastritis results from the loss of fundic glands, which produce both zymogens, and the appearance of metaplastic pyloric glands, which produce only pepsinogen II.