The prevalence of drug abuse has been reported to be up to 17.0% in Iran. The aim of this study was to investigate the prevalence of two frequently abused substances--cannabis and opium--in samples of the young population in Isfahan, Iran. In a survey done from January 2005 to December 2006, 537 individuals aged 13-20 years were recruited using a multistage probability sampling method. Demographic and clinical data were recorded through face-to-face interviews, physical examinations, and reviews of the patients' medical records by trained interviewers. Morphine and cannabis were detected by Enzyme-Linked Immunosorbent Assay (ELISA) on each blood sample. The rates of morphine and cannabis abuse were 2.2% and 3.2%, respectively. They were abused in 0.5% and 15.3% of cigarette smokers as well. Male-to-female ratio in addicts was 4:1, and the mean age of addicts was 17.54 plus or minus 1.86 years old. There was a significant relationship between male gender and addiction (P = 0.002). The prevalence of substance abuse in urban and rural areas was 6.3% and 9.5%, respectively. A total of 2.5% of rural females were addicted, compared to 2.4% in Isfahan (city). In Isfahan, opium was the most commonly abused substance while in rural areas cannabis was the most commonly abused. Substance abuse among adolescents has increased dramatically and has a significant negative effect on society. It seems that substance abuse is more prevalent than it is estimated. Therefore, developing and implementing appropriate solutions for solving this problem seems necessary. (Contains 1 table.)