The purpose of this study was to identify co-morbidity in a national sample (N=1408) of males and females entering treatment for opioid abuse. Our sample was primarily white, lived in small urban, suburban or rural locations (80%), and was well-educated. Chronic pain was a symptomatic feature in over 60% of all subjects. Furthermore, 79% of male and 85% of female prescription opioid abusers indicated that their first exposure to an opioid was a legitimate prescription for pain which subsequently led 60-70% to misuse to get high. Our data also indicate that the use of prescription opioids to get high represents the end stage on a continuum of substance abuse, beginning at a very early age. The age of first alcohol use, getting drunk, smoking, use of marijuana, stimulants and other non-opioid prescription or illicit drugs occurred very early (13-19) in prescription opioid misusers/abusers, whose first use of opioids did not occur, on average, until age 22. Finally, most of the sample had sought treatment 3 or more times for substance abuse prior to the treatment admission in which the survey was completed. Physical and mental health were very poor in both male and female prescription opioid abusers, but females were more ill and dysfunctional than males in all physical and particularly emotional domains. Our results suggest that a small number of "at risk" opioid naive pain patients, who might abuse their therapeutically appropriate opioid analgesics, can be identified by assessing pre- and co-morbid substance abuse and significant psychopathology.