In the 1970s, three randomized trials, each involving approximately 10,000 male subjects, were carried out to determine the value of lung cancer screening in cigarette smokers. These studies have been widely interpreted as providing strong evidence that screening does not contribute to decreased death rates, and, accordingly, the American Cancer Society firmly recommends against lung cancer screening. No randomized trial, however, has evaluated screening for lung cancer in women, who currently comprise 39% of the lung cancer population. The trials performed at Memorial-Sloan Kettering and at Johns Hopkins were designed so that subjects were randomized to either a single screen (annual chest x-ray alone) or a dual screen (annual chest x-ray and every-4-month sputum cytology) group. While the results of both revealed no difference in mortality between the groups, these studies were designed to examine the value of sputum cytology, and no conclusion regarding the efficacy of chest x-rays can be inferred. In the Mayo Lung Project, patients were randomized to a screened group in which a chest x-ray and sputum cytology were obtained every 4 months or to a control group in which an annual chest x-ray and cytology were simply recommended. The results indicate that after 6 years, more lung cancers were detected among the 4,618 men in the screened group (206 cases, 4.46%) than in the 4,593 men in the control group (160 cases, 3.48%). The screened group showed a superiority over the control subjects in resectability rate (46% vs 32%) and 5-year survival (33% vs 15%). However, the number of cancer deaths was slightly greater in the screened (122) than in the control group (115), and, consequently, the mortality rates were not significantly different among the groups. An "overdiagnosis bias" has been suggested to account for the increased number of lung cancers detected in the screened vs the control population in the Mayo Lung Project. This explanation is statistically plausible, but, given the status of lung cancer as the most lethal of malignancies, is biologically unlikely. An alternative hypothesis is that chance alone might have accounted for the observed 0.98% difference in lung cancer detection rates. Were this the case, then 46 additional cases would have been detected in the control group had this chance event not occurred.(ABSTRACT TRUNCATED AT 400 WORDS)