Serum group I pepsinogen (PG I) levels have been determined by radioimmunoassay in 924 subjects. The mean levels in 300 healthy control subjects and in 389 hospitalized controls were 110.6 and 100.0 ng per ml, respectively. The "normal" range is estimated to be between 50 and 175 ng per ml. The mean level of serum PG I in 7 patients with Zollinger-Ellison syndrome was 503.9 ng per ml; values ranged between 315 and 921 ng per ml. The 77 patients with duodenal ulcer had a mean serum PG I level of 221.3 ng per ml; 49 (63.6%) had values greater than 175 ng per ml. The distribution of serum PG I values was bimodal in the patients with duodenal ulcer whereas it was unimodal in both groups of control subjects. Mean serum PG I levels in 13 patients with both duodenal and gastric ulcer and in 18 patients with prepyloric ulcer were, respectively, 177.2 and 179.4 ng per ml. Approximately one-half of these patients had high values. The 28 patients with gastric ulcer had a mean serum PG I level of 116.6 ng per ml; 6 (21.4%) had high values. With the exception of 3 patients with gastric ulcer, none of the 136 patients with peptic ulcer had a low (less than 50 ng per ml) level of serum PG I. In 37 patients with chronic alcoholism the mean level of serum PG I was 73.4 ng per ml. The observed gradient in the mean level of serum PG I among the groups of patients studied is similar to that which has been reported for maximally stimulated gastric acid output. This finding suggests that the secretory potential of the fundic gland mucosa of the stomach may be reflected by the level of PG I in serum.