Sequential paraffin sections of 222 epithelial lung tumors comprising all common histologic types, and 31 pleural mesotheliomas of all variants were immunostained with monoclonal antibodies (Mabs) B72.3 and CSLEX-1. Reactivity with Mabs B72.3 and CSLEX-1 respectively was noted in 7/57 and 4/57 squamous carcinomas, in 44/70 and 60/70 adenocarcinomas, 9/16 and 11/16 bronchioloalveolar carcinomas, 8/25 and 14/25 large cell undifferentiated carcinomas, 3/3 and 3/3 adenosquamous carcinomas, 0/11 and 0/11 carcinoids, 0/10 and 2/10 well differentiated neuroendocrine (NE) carcinomas, 4/13 and 5/13 intermediate cell NE carcinomas, 0/17 and 0/17 small cell NE carcinomas, and 0/31 and 1/31 mesotheliomas. In most instances, both Mabs stained the same tumors; however, reactivity with CSLEX-1 was more intense and extensive, and involved more cases. Therefore, regardless of conventional histologic type, staining with Mabs B72.3 and CSLEX-1 defines 4 subsets of lung tumors: one expressing both antigens, two expressing one but not the other, and one expressing neither. The possible biological and/or clinical significance of these subsets remains undetermined. When correlated with conventional histologic tumor types, our findings indicate: 1). both of these Mabs recognize most but not all adenocarcinomas and bronchioloalveolar carcinomas, and since CSLEX-1 stained more cases than B72.3, it may be argued that the former is a broader exocrine phenotype marker than the latter; 2). both of these Mabs select exocrine subsets of large cell undifferentiated carcinomas; 3). both of these Mabs stain exocrine cell subpopulations in well differentiated and intermediate cell NE carcinomas but not in carcinoids or small cell NE carcinomas, and 4). except for rare cases, neither B72.3 nor CSLEX-1 reacts with mesotheliomas regardless of variant.(ABSTRACT TRUNCATED AT 250 WORDS)