We studied the effect of smoking on tumor progression in 3312 patients with lung cancer registered at the National Matsudo Hospital and National Cancer Center Hospital East between 1977 and 1996. The odds ratios of the following variables for tumor extent (localized versus advanced disease) and hazard ratios for survival were calculated in both sexes separately using the logistic regression and Cox proportional hazard models, respectively: smoking history, number of cigarettes smoked per day, pack-years smoked, age, histological type, and the year of admission. Of the 943 women, 367 (38.9%) were smokers and 694 (73.6%) had adenocarcinoma, whereas of the 2369 men, 2255 (95.2%) were smokers and 1010 (42.6%) had adenocarcinoma. In female adenocarcinoma patients, the odds ratio (95% confidence interval) for advanced disease and the hazard ratio (95% confidence interval) for survival with an increase of 30 cigarettes smoked per day were 2.86 (1.49-5.49) and 1.52 (1.13-2.04), respectively, but in those with non-adenocarcinoma, the odds ratio and hazard ratio were 0.96 (0.41-2.23) and 1.13 (0.75-1.70), respectively. In male patients, smoking history influenced tumor progression regardless of histological type, but the odds ratios and hazard ratios were lower than those for women with adenocarcinoma. In conclusion, smoking habit was closely correlated with progression of adenocarcinoma in women. This association was not observed in women with non-adenocarcinoma and was weaker in men, suggesting various effects of smoking on lung cancer development depending on gender and the histological type of the tumor.