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Precursors of the gastric proteases pepsinogen A (pepsinogen I) and pepsinogen C (pepsinogen II) and slow-moving protease were demonstrated in biopsy specimens from Barrett's epithelium in 21 of 22 patients with Barrett's esophagus; in 14 of them, in variable combinations at different sites. In 13 of 19 patients (68.4%) with detectable pepsinogen A, different isozymogen patterns were found between the Barrett's epithelium and the gastric corpus mucosa. Discrepancies consisted mainly of a stronger pepsinogen 5 band in the Barrett's epithelium, with a higher incidence in biopsy specimens with features of dysplasia than with no or indefinite dysplasia; the difference was, however, not statistically significant. Zymograms of 69 biopsy specimens from Barrett's epithelium were correlated with the histologic type: pepsinogen A and C were most frequently found in the fundic type, least often in the specialized intestinal type. In control gastric corpus biopsy specimens, pepsinogen A and C as well as slow-moving protease were always detectable. The observed variability of gastric protease patterns, in particular of pepsinogen A isozymograms, may be due to differences in expression within the pepsinogen A cluster, suggesting a deregulation of gene expression or partial deletion of the pepsinogen A gene cluster.