A population-based case-control study on laryngeal cancer was conducted from 5/1998 to 12/2000 with 257 cases and 769 controls in south-west Germany to investigate the effect of smoking, alcohol, occupational and molecular-genetic risk factors. 50.6% of the tumors were glottis or subglottis, 17.5% supraglottis. The subsite of 31.9% of the tumors could not be determined clearly due to advanced stage. The risk increased in relation to the number of packyears (pck): OR(odds ratio)=10.1 for 10-20 pck, p<0.001, 95% confidence interval (CI) 4.1-24.7, and in case of strong smoking (> 80 pck) OR=59.8, 95% CI, (21.3-167.3). Cancer risk is reduced for ex-smoking (> 2 years) OR=0.36, 95% CI 0.24-0.53. The risks were higher for supraglottis than for glottis and subglottis tumors. The effect of alcohol is lower. A significantly increased odds ratio of 2.0, 95% CI (1.0-3.9) results for 75-100 g ethanol/day only for glottis & subglottis tumors. The OR rises from 2.2, 95% CI (1.1-4.3) for 100-150 g ethanol/day to 4.3, 95% CI (1.4-13.2) for more than 150 g ethanol/day (all models adjusted for education). As the best model for a common dose response relationship with consideration of interaction between smoking and alcohol results OR(x, y, z) = exp(0.95 * x -1.0 * y + 0.13 * z -0.024 * x * z), with x=smoking (in ln(pck+1)), y=ex-smoking (>2 years), z=alcohol (in 10g/day). The interaction term between both factors is negative (p=0.027). For example the risk for a smoker with 50 pck and 100 g ethanol/day results an OR of 57.5. On these assumptions for men and women more than 90% of the tumors can be led back to smoking. Contrary to earlier investigations we observe a sub-multiplicative common effect of smoking and alcohol, which is well supported due to the high number of cases. Due to the strong single effects the risk for persons with high alcohol and tobacco consumption is extremely high which indicates the importance of intervention.