The present study provides an assessment of the importance of tobacco and alcohol consumption upon the development of oral epithelial dysplasia (OED) in a large group of European patients. Data were collected in a case-control study based upon 630 patients with OED and 643 control subjects selected from UK dental hospital patients with oral disease not caused by tobacco or alcohol. Logistic regression was used to determine the association of several independent factors on the risk of OED. No relationship emerged between patient's gender, age or ethnicity and risk of OED. The regression model demonstrated a combined effect of tobacco smoking and alcohol drinking upon the risk of OED. Non-filter cigarette smoking was a significant predictor of OED, as was alcohol consumption, and the two habits compounded one another in the overall risk of disease. When both factors combined were included in the model through interaction terms, their individual impact was only moderately reduced, illustrating the importance of both factors in their own right. However, more detailed analysis of tobacco smoking habits revealed that the increased risk of OED from smoking was largely attributable to heavy smoking (20 cigarettes per day, OR = 4.38, 95% C.I. = 2.6, 7.2) especially non-filter cigarettes (OR = 1.95, 95% C.I. = 0.9, 4.0) relative to non-smoking. Both heavy smoking and non-filtered tobacco were higher risks for OED than alcohol consumption alone. Tobacco cessation was associated with a significant decline in risk of OED, the reduction being rapid and marked. For alcohol consumption the association with OED was considerably stronger for drinkers of fortified wines and spirits (OR = 3.75, 95% C.I. = 1.40, 10.05 and OR = 1.36, 95% C.I. = 0.76, 2.45, respectively). It is concluded that, while tobacco and alcohol synergistically influence the development of OED, exclusive tobacco consumption is more likely than exclusive alcohol consumption to give rise to OED. The risk of OED may thus be significantly reduced by behavioural changes such as moderation of tobacco and alcohol use.