Murine monoclonal antibody B72.3, prepared against a membrane-enriched extract of human metastatic carcinoma, was reacted with a spectrum of adult and fetal human tissues using avidin-biotin-complex immunohistochemical techniques to evaluate the expression of the reactive tumor associated glycoprotein (TAG)-72 antigen. TAG-72 was shown to be expressed in several epithelial-derived cancers including 94% of colonic adenocarcinomas, 84% of invasive ductal carcinomas of the breast, 96% of non-small cell lung carcinomas, 100% of common epithelial ovarian carcinomas, as well as the majority of pancreatic, gastric, and esophageal cancers evaluated. TAG-72 expression was not observed, however, in tumors of neural, hematopoietic, or sarcomatous derivation, suggesting that the TAG-72 antigen is "pancarcinoma" in nature. Appreciable monoclonal antibody B72.3 reactivity was generally not observed in adult normal tissues, with limited reactivity noted in a few benign lesions of the breast and colon. TAG-72 antigen expression was detected, however, in fetal colon, stomach, and esophagus, thus defining TAG-72 as an oncofetal antigen. TAG-72 has previously been shown to be distinct from carcinoembryonic antigen and other tumor associated antigens. The pancarcinoma distribution and lack of significant reactivity with normal adult tissues of monoclonal antibody B72.3 suggest its potential diagnostic and therapeutic utility for human carcinomas.