OBJECTIVE: The authors examined trends in the prevalence of substance use and its relationship to attributes of life style among college students over a 30-year period. METHOD: They distributed anonymous questionnaires to 796 seniors at a large New England college in 1999, using methods essentially identical to those of their previous studies at the same college in 1969, 1978, and 1989. RESULTS: Most forms of drug use rose to a peak in 1978 then fell over the next 21 years, except for use of 3,4-methylenedioxymethamphetamine ("ecstasy"). On several variables, college substance users differed more sharply from nonusers in 1999 than in previous decades. CONCLUSIONS: Although the study was limited to students at a single institution, its findings suggest that college drug use is generally declining and that users have increasingly diverged from nonusers in their values and life style.