The Trilogy Project is a longitudinal study of lesbian and gay people living in and around two metropolitan areas in a southern state. The study was specifically designed to provide (1) epidemiological data on the lifetime, past year, and past month prevalence rates for the use of 6 illicit, 4 psychotherapeutic, and 2 licit drugs, and (2) comparative data to the National Household Survey on Drug Abuse (NHSDA). Self-report data were collected on 1067 respondents using multiple sampling strategies and a research design that yielded response rates averaging over 50%. Results indicated some age group differences in the prevalence of certain drugs by gay men compared to lesbians. When comparisons were made to the NHSDA, Trilogy Project respondents were found to have significantly higher prevalence rates for the past year use of marijuana, inhalants, and alcohol but not cocaine. While lesbian and gay people drink alcohol more frequently during the month than NHSDA respondents, few differences occurred between the two samples for heavy alcohol consumption. Research questions suggested by the data and theoretical directions for future research are discussed.