P68 is a protein kinase expressed by eukaryotic cells, which is inducible by alpha interferon, and is believed to be an important factor in the regulation of viral and cellular protein synthesis. We have previously reported on a monoclonal antibody, TJ4C4, which is able to specifically detect p68 in formalin-fixed, paraffin-embedded tissue. Because of its important role in regulating cellular protein synthesis, we hypothesized that p68 expression would vary among lung neoplasms with level of differentiation and degree of biosynthetic activity. A total of 246 untreated primary pulmonary and pleural neoplasms were studied. The frequency and relative intensity of p68 expression was determined by light microscopic evaluation of ABC immunoperoxidase stained specimens. All categories of tumors studied demonstrated a spectrum of p68 expression. Expression of p68 correlated well with degree of differentiation in squamous cell carcinomas (SQCC) and acinar adenocarcinomas (AAC). Papillary adenocarcinoma (PAC) and bronchioalveolar carcinoma (BAC) expressed low levels of p68, despite their well differentiated appearance. Expression of the antigen in large cell carcinoma (LCC) was higher than that seen in either poorly differentiated AAC or SQCC. Neuroendocrine tumors generally showed low levels of p68 expression with the intermediate variant of small cell carcinoma expressing higher levels of p68 than the classic "oat cell" form (SCC). Carcinoid tumors expressed higher levels of p68 than did atypical carcinoid tumors. Mesotheliomas showed weak expression of p68, limited primarily to areas of glandular differentiation in the epithelioid form.(ABSTRACT TRUNCATED AT 250 WORDS)