FOR THE PAST 25 YEARS, the US has pursued a drug policy based on prohibition and the vigorous application of criminal sanctions for the use and sale of illicit drugs. The relationship of a prohibition-based drug policy to prevalence patterns and health consequences of drug use has never been fully evaluated. To explore that relationship, the author examines national data on the application of criminal penalties for illegal drugs and associated trends in their patterns of use and adverse health outcomes for 1972-1997.Over this 25-year period, the rate at which criminal penalties are imposed for drug offenses has climbed steadily, reaching 1.5 million arrests for drug offenses in 1996, with a tenfold increase in imprisonment for drug charges since 1979. Today, drug enforcement activities constitute 67% of the $16 billion Federal drug budget and more than $20 billion per year in state and local enforcement expenditures, compared with $7.6 billion for treatment, prevention, and research.Despite an overall decline in the prevalence of drug use since 1979, we have seen dramatic increases in drugrelated emergency department visits and drug-related deaths coinciding with this period of increased enforcement.Further, while black, Hispanic, and white Americans use illegal drugs at comparable rates, there are dramatic differences in the application of criminal penalties for drug offenses. African Americans are more than 20 times as likely as whites to be incarcerated for drug offenses, and drug-related emergency department visits, overdose deaths, and new HIV infections related to injecting drugs are many times higher for blacks than whites.These outcomes may be understood as public health consequences of policies that criminalize and marginalize drug users and increase drug-related risks to life and health.