The purpose of this exploratory study was 3-fold: (a) to determine how 'spirituality' is defined by inner-city HIV-positive drug users; (b) to determine perceived relationships between spirituality and abstinence, harm reduction, and health promotion; and (c) to assess interest in a spirituality-based intervention. Opioid-dependent patients enrolled in an inner-city methadone maintenance program participated in the study; 21 participated in focus groups and 47 completed a questionnaire. In the focus groups, two predominant themes emerged: spirituality as a source of strength/protection of self, and spirituality as a source of altruism/protection of others. A large majority of the larger sample expressed an interest in receiving spirituality-focused treatment, reporting that such an intervention would be helpful for reducing craving and HIV risk behavior, following medical recommendations, and increasing hopefulness. African American women perceived spirituality as more helpful in their recovery than did African American men.