As the largest randomized clinical trial conducted by the National Institute of Mental Health, the Multimodal Treatment Study of Children with ADHD (MTA) will yield data on a diverse sample of 576 7.0- to 9.9-year-old children with attention-deficit hyperactivity disorder (ADHD), Combined type, regarding the relative and combined effectiveness of psychosocial and pharmacologic interventions. After delineating key challenges posed by such a multisite investigation, we describe the MTA's multiple-gating procedures for recruitment, screening, and diagnosis of a diverse sample. We then discuss the cross-domain assessment battery for tracking the sample before, during, and after 14 months of active intervention. Throughout, we emphasize the guiding principles that shaped pertinent decision making. Highlighted are issues of psychometric adequacy; dimensional vs. categorical measurement; multi-method, multi-agent, and multi-domain coverage; plotting of individual trajectories of development and change; respondent bias and burden; appraisal of treatment processes as well as outcomes; and construction of composite indices.