The immunohistochemical expression of pepsinogen I (PI) and pepsinogen II (PII) was studied in 103 gallbladder carcinomas, 25 non tumoral gallbladder lesions and 23 gallbladder cancer metastases. PI was positive in 6% of carcinomas and only in 2% of non tumoral contiguous mucosa. PII was positive in 46% of carcinomas and 43% of controls. Metastases were negative for both enzymes. Pyloric gland metaplasia of non tumoral mucosa adjacent to the tumor expressed PII in 68.9% and PI in 3.4% of cases. The same lesion in non tumoral gallbladders was positive for PII in 66.6% of cases, and no case expressed PI. There was no relationship between PI expression and the histological degree of differentiation. Only tumors with serosal or subserosal involvement were positive for PI. PII had a higher expression in early or well differentiated tumors. Tumors with pyloric gland metaplasia in the contiguous non tumoral mucosa expressed PII more frequently. Our results, based on the expression of PI and PII, suggest a relationship between the presence of pyloric gland metaplasia and some types of gallbladder cancer.