Universal screening for autism spectrum disorder (ASD) is recommended during pediatric primary care visits in the first 2 years of life. However, many children are missed by initial screening and not diagnosed with ASD until years later. Research efforts are underway to develop and evaluate new objective measures of risk for ASD that can be used in infancy, before symptoms emerge. Initial studies with these tests, particularly MRI-based screening for infants at high familial risk, have shown promise but have not yet been evaluated in clinical trials. We present the study design for a hypothetical clinical trial that would combine presymptomatic detection and intervention for ASD and consider, through commentaries from diverse perspectives, the ethical issues that should be anticipated in advance of beginning such trials. Commentators Drs Pruett and Piven address the social value of the proposed research and importance of researcher-bioethicist collaborations. Drs Estes and Wolff discuss the clinical potential and challenges of developing presymptomatic interventions for infants at risk for ASD. Dr Harrington takes a neurodiversity view of presymptomatic prediction and intervention and their implications for autistic identity and quality of life. Finally, Drs MacDuffie, Peay and Wilfond consider the potential risks and benefits that must be evaluated and weighed in the next phases of research on presymptomatic detection and intervention for ASD.