A case-control study was conducted to investigate the relative risk of cancer detection among Du Pont employees who worked in a tetraethyl lead (TEL) manufacturing area. The study's objective was to determine whether the employees' risk of developing or dying from cancer was associated with occupational exposure to TEL. All malignant neoplasms detected in the active and pensioned employee population during the period 1956-1987 were studied. TEL exposure was estimated by the following measures: ever employed in the TEL area, years of employment in TEL, TEL exposure rank, and the TEL cumulative exposure index. TEL manufacturing exposed employees to both organic and inorganic lead compounds. Because the underlying data did not permit the exposure assessment to distinguish between organic and inorganic lead, the TEL exposure measures reflect exposure to the TEL manufacturing process itself. The effects of latency, cigarette smoking habits, and exposures to other known or suspected carcinogens at the plant were also assessed. A strong association was observed between exposure to the TEL manufacturing process and rectal cancer (the odds ratio was 3.7 with 90% confidence limits of 1.3-10.2 for the analysis of ever/never exposed to TEL). An exposure-response relationship was noted with a fourfold elevation in the odds ratio at the high-very high cumulative exposure level. These patterns were even more pronounced after assuming a 10 year latency. Similar results were obtained for cancers of the sigmoid colon. These findings suggest that exposure to the TEL manufacturing process may have played a causal role in the colorectal cancer experience at the plant. This position is supported by the graded exposure-response relationships, the consistency of the results across exposure measures, the specificity of the health outcome (i.e., colorectal cancer), and the strength of the association. However, the evidence for causality is not compelling. This is the first report of an association between TEL manufacturing and colorectal cancer, and the evidence is compatible with a wide range of causal (i.e., indirect vs. direct acting; initiating vs. promoting) and noncausal (i.e., statistical and methodological bias; coincidence) interpretations.