Substance use in mentally ill patients is now a major problem that influences the course and outcome of psychosis. With prevalence ranging up to 60 percent, several theories were postulated to explain the link. It would be interesting to know if substances have different effects in persons with psychosis than in those without. This study aimed to explore patterns of symptomatology of dependence and comorbid psychiatric illness by comparing and contrasting it with a group suffering from pure substance dependence. Consecutively admitted patients who were matched for age, sex, and tobacco use were divided into three groups. These were substance dependence without any comorbid psychiatric disorder (SD; n = 32), schizophrenia with substance dependence (SC; n = 31), and bipolar disorder with substance dependence (BD; n = 31). Patients were administered the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and Mini International Neuropsychiatric Inventory (MINI) to evaluate the chronology of criterion of International Classificiation of Diseases (ICD)-10 dependence. Results showed that cannabis was the most common substance used by both the SC (100 percent) and BD (80 percent) groups. This was followed by alcohol as the most common substance used, with prevalence of 87 percent in SC and 77 percent in BD groups. There was a significant difference in the pattern of use of cannabis in patients with psychosis, who developed tolerance much faster (P = .018) and had longer durations of cannabis use (P = .001) than the SD group. The presence of "loss of control" over drug use criterion seems to be a specific marker predicting development of dependence and psychosis. Cannabis use is more strongly associated with development of psychosis than any other substance. Tables, figures, and references (Published Abstract)