Forty-eight percent of the sample (n=1,086) reported no lifetime use of the 4 categories of prescription drugs (nonusers); 31.5 percent reported medically prescribed use only (medical users); 17.5 percent reported both medical and nonmedical use (medical/nonmedical users); and 3.3 percent reported nonmedical use only (nonmedical users). Multivariate analyses showed that medical/nonmedical users and nonmedical users were significantly more likely than nonusers to report illicit drug use and probable drug abuse. Medical users generally reported similar or increased likelihood of illicit drug use and probable drug abuse compared with nonusers. These findings show that nonmedical use of prescription drugs is a problem among secondary school students. The study was conducted during 1 week in May 2005, drawing on the entire population of 1,594 middle-school and high-school students (7th through 12th grades) from a public school district in the Detroit metro area. A self-administered Web-based survey took approximately 22 minutes to complete. A participation rate of 94 percent was achieved. The questionnaire solicited information on the respondent's medical use of specified prescription medications, the nonmedical use of prescription medications, prescription drug-use status, and drug abuse as determined by the Drug Abuse Screening Test. 4 tables and 28 references