BACKGROUND: Research involving decisionally incapable adults remains an unsettled and controversial policy issue, especially for protocols that involve significant risk to participants. Few data exist to guide policymakers and IRBs OBJECTIVE: Survey the views of persons at heightened risk for dementia regarding the acceptability of surrogate consent for biomedical research of varying levels of risks and potential benefits. METHODS: Using a mail survey, the authors surveyed the participants at one of the sites of the Alzheimer's Disease Anti-inflammatory Prevention Trial (all participants are 70 years old or older with at least one first-degree relative with dementia) and measured responses regarding the acceptability of surrogate consent for 10 research scenarios of varying degrees of risks and benefits (ranging from an observation study to a gene transfer protocol), given from the perspectives of social policy, personal preferences for self, and preferences when deciding on behalf of a loved one. RESULTS: Two hundred twenty-nine of 259 eligible participants responded (88%). A large majority (>90%) found minimal risk studies as well as randomized clinical trials of new medications acceptable for surrogate consent. A smaller majority found the more invasive studies acceptable. Participants were more cautious when deciding for a loved one. General attitude toward biomedical research and scenario-specific risk perception were strong independent predictors. Demographic and personal history variables had relatively little effect. CONCLUSIONS: Laypersons at heightened risk of Alzheimer disease discriminate among research scenarios of varying risks and burdens. They are supportive of surrogate consent-based research even when the risks and burdens are significant to the subjects; these opinions appear to be based in part on their assessment of risks as well as on their general attitude toward biomedical research.