Monoclonal antibodies (MAbs) COL-4 and COL-12, to the carcinoembryonic antigen (CEA), and B72.3, CC-49, CC-83, to the tumor-associated glycoprotein 72 (TAG-72), were used to study the expression of distinct epitopes of the two molecules in 71 cases of lung carcinoma of differing histotype. These MAbs reacted with the majority of adenocarcinomas by immunoperoxidase on tissue sections, but demonstrated a more restricted reactivity with squamous carcinomas. MAb CC-49 detected the highest percentages of adenocarcinoma cells while the B72.3 epitope was expressed more in squamous carcinoma cells. No significant reactivity with any of these MAbs was observed in small cell carcinomas. The expression of the CEA and TAG-72 epitopes in non-small cell lung cancers was highly heterogeneous: a distinct epitopes in non-small cell lung cancers was highly heterogeneous: a distinct epitope could be expressed by the majority of cells, whereas another of the same antigenic molecule was either poorly or not expressed. In adenocarcinomas, mixtures of anti-CEA, anti-TAG-72, and anti-(TAG-72 plus CEA) MAbs resulted in additive reactivity with an increase of the immunopositive tumors and of the percentages of immunostained cells. This was particularly evident for the anti-(TAG-72 plus CEA) mixture. In squamous cell carcinomas the increase was modest and was mainly related to anti-TAG-72 reactivity. These studies suggest variability in the antigenic structure of tumor-associated antigens expressed by carcinomas and indicate that anti-(TAG-72 plus CEA) mixtures may represent an immunological adjunct for clinical application in adenocarcinoma patients. On the other hand, TAG-72 should be considered a better target antigen, as compared to CEA, in the detection of squamous cell carcinomas.