Mentally disabled adults often serve as subjects in research on mental illness, developmental disabilities, dementia, and other conditions associated with mental impairment. Since US regulatory policy fails to resolve many ethical issues presented by such research, investigators and institutional review boards must determine the appropriate standards and procedures for studies involving adults with mental disabilities. Procedures for capacity assessment and information disclosure should enhance the autonomy of capable subjects and accurately identify subjects incapable of independent choice. Research teams should inform proxy decision makers of their ethical responsibilities. Decisionally incapable adults objecting to research involvement should rarely be included in studies. Researchers, institutional review boards, advocacy groups, and federal officials should collaborate to improve evaluation of risks and potential benefits to decisionally incapable subjects. These groups should also seek consensus on appropriate risk limits in studies presenting no prospect of direct benefit to decisionally incapable subjects. Finally, subject populations should be represented in research planning and review activities.