Underage drinking and drug use among college students are major public health concerns, yet few studies have examined these behaviors and their associated risk factors and consequences prospectively. This paper describes the sampling and recruitment methods of a longitudinal study of 1253 college students at a large, mid-Atlantic university. Incoming first-year students were screened during the unique window between high school and college in order to oversample drug users for longitudinal follow-up. Intensive recruitment strategies yielded a 95% cumulative response rate in annual interviews and semiannual surveys. The authors report preliminary results on exposure opportunity, lifetime prevalence, initiation, continuation, and cessation of substance use for alcohol, tobacco, and 10 illicit and prescription drugs during the first 2 years of college. Findings suggest that although some substance use represents a continuation of patterns initiated in high school, exposure opportunity and initiation of substance use frequently occur in college. Implications for prevention and early intervention are discussed. (Contains 1 note, 4 tables, and 4 figures.)