The prognostic implication of atypical squamous metaplasia of the respiratory tract has been uncertain, especially for mild atypia. The relation between degree of severity of atypical metaplasia as detected by sputum cytology and incidence of bronchogenic carcinoma was assessed among 14,414 men aged 45 years or older who smoked one or more packs of cigarettes per day. Trial participants underwent sputum cytologic evaluations every 4 months for an average of 7.4 years as part of the Cooperative Early Lung Cancer Detection Program of the National Cancer Institute and were followed for the development of lung cancer between 1971 and 1983 at three institutions: The Johns Hopkins University, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Analysis with logistic regression controlling for age, race, occupational exposures to lung carcinogens, average number of cytology records per year, and smoking habits revealed that the estimate of the relative rate (RR) of developing bronchogenic carcinoma was greater among men who had mild atypia as compared with men who had negative cytology readings, but there were marked differences among institutions (RR = 1.1, 95% confidence interval (Cl) 0.8-1.5 at The Johns Hopkins University; RR = 1.6, 95% Cl 1.1-2.5 at the Memorial Sloan-Kettering Cancer Center; and RR = 2.5, 95% Cl 1.6-4.0 at the Mayo Clinic). Results suggest that mild atypia as detected by cytologic evaluation of sputum is an indicator of a modest elevation in risk of bronchogenic carcinoma.