In the Smokers and Nonsmokers Study, the authors investigated the feasibility of using random digit dialing telephone interviews to locate adults in the continental United States who were willing to provide DNA from buccal swabs through the mail. Interviews with 3,383 adults regarding their smoking-related behaviors (response rate = 70%) were conducted in 1999-2000; swab returns continued into early 2001. Overall, 57% of interviewees agreed to receive mailed information explaining the study. Better-educated persons (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.6), younger persons (OR = 0.988, 95% CI: 0.983, 0.992), persons with symptoms of depression (OR = 1.8, 95% CI: 1.4, 2.4), and current smokers (OR = 2.25, 95% CI: 1.8, 2.8) were likelier to agree to receive a mailing. Approximately 26% of interviewees (45% of those receiving kits) returned buccal swabs, and 18% were successfully genotyped. Older (OR = 1.02, 95% CI: 1.01, 1.03), better-educated (OR = 1.4, 95% CI: 1.1, 1.7), and White (OR = 1.8, 95% CI: 1.4, 2.5) participants were more likely to return DNA samples, but current smokers (OR = 0.6, 95% CI: 0.5, 0.8) were less likely to do so. Participants were randomly assigned to one of two forms of participation: the "registry" group (names were kept on file) or the "made-anonymous" group (names were unassociated with samples). The two groups were equally likely to return kits, but registry respondents were more likely to nominate siblings for participation in the study (OR = 1.6, 95% CI: 1.2, 2.1). The participants in this study were similar demographically to the national population. The authors conclude that random digit dialing surveys coupled with mail collection of DNA may constitute a practical method of obtaining DNA samples for biobehavioral research.