The aim of this study was to improve understanding of smokers' potential reactions to genetic testing for smoking-related diseases. One thousand twenty-four respondents completed a postal survey; 186 were smokers. Questions addressed anticipated psychological and behavioral reactions to genetic test results using hypothetical scenarios. Of smokers, 65% anticipated being motivated to quit smoking upon receiving a positive genetic test result; 39% anticipated being demotivated by a negative result. More smokers anticipated being depressed in response to receiving a positive result for cancer than for heart disease (40% vs. 24%). Anticipated motivation was associated with higher desire to quit and lower nicotine addiction, anticipated depression with poorer understanding of genetic testing, and anticipated demotivation with lower education. Smokers who have a high desire to quit may use genetic testing as a motivational tool. Understanding of genetics may be important in determining how individuals respond to genetic tests for complex diseases. (Contains 5 tables and 1 figure.)