The interaction between aetiological factors (e.g. tobacco smoke) and target cells in lung tissues is modulated by host factors, leading to variable risk among individuals. We have studied some of the metabolic properties of the human lung and the effects on them of tobacco smoke. The activity of activating enzymes is induced by recent tobacco smoke exposure, whereas that of inactivating enzymes is depressed, and this effect is greater in patients with lung cancer than in controls. This imbalance between activating and detoxifying enzymes in the lung may be a key factor in determining the genetic damage to the lung. These differences between lung cancer patients and controls in metabolic activities in lung tissues may be documented at a phenotypic level as well as at a genotypic level. Also wide interindividual differences have been shown in deoxyribonucleic acid (DNA) repair enzymes and in the extent of DNA damage.