We conducted a registry-based case-control study to examine the relation between smoking and lung cancer by gender and histologic type. Our analyses were based on 14,596 cases and 36,438 age-matched controls. Relative risk associated with ever-smoking, and level of smoking was consistently higher in females than males for all lung cancers combined (ever-smoking odds ratios: 12.7 for females and 9.1 for males) and for each histologic type except adenocarcinoma. Female-male differences in relative risk were larger in younger age groups. The largest estimates of the attributable fraction due to smoking were observed for small cell carcinoma (97% in females and 91% in males); conversely, the smallest value was noted for adenocarcinoma (86% in females). Although our study was unable to measure absolute risk, our findings, other recent studies, and contemporary female smoking patterns raise concerns that female smokers may assume a proportionally greater burden of lung cancer morbidity and mortality in the future.