This study examined alcohol and licit and illicit drug use in a highly educated workforce. A comprehensive health survey of a 10% random sample of a workforce (n = 8,567) yielded a 60% response rate (n = 504) after accounting for 15 undeliverable surveys. Many respondents reported past-year use of alcohol (87%). Thirteen percent of respondents consumed three or more drinks daily; 15% were binge drinkers. Twelve percent of the workforce was assessed as having a high likelihood of lifetime alcohol dependence; 5% of respondents met criteria for current problem drinking. Overall, 42% reported using mood-altering prescription drugs (analgesics, antidepressants, sedatives, or tranquilizers). Eleven percent reported using illicit drugs (cocaine, hallucinogens, heroin, or marijuana) in the past year. Significant relationships were found between gender, age, ethnicity, and occupation with some measures of alcohol consumption and use of mood-altering drugs. These results indicate prevention and early intervention programs need to address use of mood-altering substances (including alcohol) in highly educated workforces.