Background: Psychotic symptoms (delusions and hallucinations) are reported to be increased among persons using illicit substances, but little is known about the comparative frequency with which the symptoms occur with abuse of different substances. To establish this, we interviewed individuals who had wide experience of commonly used drugs. Methods: Four hundred seventy-six intravenous drug users, crack-cocaine users, and heroin snorters recruited via street outreach were interviewed using the Composite International Diagnostic Interview-Substance Abuse Model to assess dependence on a number of substances including amphetamines, cannabis, cocaine, and opioids. As a part of this assessment, we assessed a history of delusions and hallucinations in the context of use of, or withdrawal from, these specific substances. Results: From 27.8% to 79.6% users of amphetamine, cannabis, cocaine, and opiates met Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, dependence for that specific substance. The prevalence of psychotic symptoms associated with each specific substance ranged from users with no diagnosis to users with severe dependence as follows: amphetamines (5.2%-100%), cannabis (12.4%-80.0%), cocaine (6.7%-80.7%), and opiates (6.7%-58.2%). The risk of psychotic symptoms increased for respondents who abused (odds ratio [OR], 12.2) or had mild (OR, 17.1), moderate (OR, 47.0), or severe dependence (OR, 114.0) on cocaine when compared to those who were users with no diagnosis. A similar pattern was evident in cannabis, opiate, and amphetamine users. Conclusions: Most users dependent on illicit substances experience psychotic symptoms in the context of use of, or withdrawal from, these substances. Psychotic symptoms increased with the severity of the substance use disorders for all 4 substances. These findings emphasize the importance of developing services to target this population as they are at a heightened risk for developing psychotic symptoms.