In a recent colon cancer risk study, genetic assessment and colonoscopy were offered to virtually all of the adult Ashkenazi Jews in an urban community. The present study was designed to examine factors influencing participation and response in the initial study and to suggest strategies for improving participation in future health promotion programs. The study comprised a random sample of three groups of individuals who had been targeted for participation in the previous study: those who had (a) agreed to participate (n = 234); (b) declined participation (n = 179); and (c) failed to respond to a mailed recruitment package (n = 128). All participants completed a brief telephone survey. Key multivariate predictors of both response and participation were individuals' perceptions of the drawbacks of participating in colon cancer screening research and the degree of decisional conflict they experienced. Response was further predicted by the influence of spouses, family history of colon cancer, past knowledge of genetic testing for colon cancer, and education level. Participation was predicted by awareness that the study was supported by the Ashkenazi Jewish community, past experience with genetic testing, individuals' perceptions of the benefits of participating, and whether or not they had children. The degree to which individuals understand the purpose and nature of genetic screening research, along with their levels of decisional conflict and other psychosocial factors, may influence the likelihood of their participation in such research. Results of this study suggest a number of possible strategies for improving participation and response rates in disease prevention and detection studies.