ABSTRACT This application is for a 5-year continuation of the national longitudinal panel data collections of the Monitoring the Future (MTF) study, an ongoing epidemiological and etiological substance use research and reporting project begun in 1975 (N~120,000, 1976-2027). In addition to being a basic research study, MTF has become one of the nation's most relied upon sources of information on trends in illicit drug, alcohol, and nicotine/tobacco use among adolescents and young, middle, and older adults in the United States. This MTF Panel application seeks to continue the longitudinal (web-based) surveys of nationally representative samples of high school students (modal age 18) at modal ages 19–30, 35, 40, 45, 50, 55, 60, and now 65. The companion MTF Main application covers in-school data collections of nationally representative samples of 8th, 10th, and 12th grade students and funding for cross-sectional and longitudinal data analysis. The Main and Panel components together comprise the integrated MTF study. MTF's broad measurement covers (a) initiation, use, and cessation for over 50 categories and subcategories of licit and illicit drugs, including symptoms of substance use disorders; (b) attitudes and beliefs about substances, perceived availability, and peer norms; (c) individual risk and protective factors (e.g., depressive affect, pro-social activities); (d) aspects of key social contexts (e.g., home, work), and social role statuses and transitions; (e) health, social, and achievement consequences; and (f) risk and protective behaviors related to the spread of HIV/AIDS. The cohort-sequential longitudinal design permits the measurement of factors that may explain historical trends and cohort differences. MTF Panel is designed to document the developmental course of drug use and related attitudes from adolescence through adulthood (ages 18-65), and to determine the predictors and consequences of drug use across the life course. Research on risk and protective behaviors for the transmission of HIV/AIDS will be a focus, extending the age of monitoring to those aged 19 to 30. Substance use by college status will continue to be tracked, totaling 45 years of annual trend data comparing college students and non-college young adults in the U.S. The long-term follow-up will now include data at age 65 among cohorts who were in high school during historic peaks in teen substance use and are now facing declining health decades later. Results will continue to elucidate drug use from adolescence through adulthood—including the use of new drugs and modalities—with important implications for national policy, research, prevention, and treatment agendas. As our nation sees increases in adolescent and adult vaping and marijuana use, the need to understand trends in use from adolescence to adulthood and consequences on health, well-being, and work and family life has never been greater.