Previous research has been inconsistent in documenting a strong relationship between depression and HIV/AIDS, although a recent meta-analysis of studies examining this issue indicates that rates of depression are modestly higher for this population. For the current study, conducted from 2001-2004, we sought to examine rates and types of depressive symptoms in a cohort of patients receiving HIV care at two urban medical centers. These patients were participants in an intervention study examining adherence and mental health in persons triply diagnosed with psychiatric disorders, substance use disorders, and HIV/AIDS. Nearly three quarters of these participants were people of color, two thirds described their sexual orientation as heterosexual, and the vast majority were unemployed. We sought to examine the relationship of depression to patients' adherence to antiretroviral medication regimens (highly active antiretroviral therapy [HAART]). Results obtained from structured clinical interviews and self-report questionnaires indicated that study participants experienced high rates of depressive symptoms, and that 72.9% of participants met criteria for major depressive disorder (MDD). The results of this study offer a detailed view of the incidence and nature of MDDs and depressive symptoms for an urban sample of substance-abusing adults with HIV/AIDS. Given the degree to which depressive symptoms and MDD appear to be prevalent for this group, as well as the observation that these symptoms are amenable to treatment, future research should focus on identifying helpful strategies and interventions for treating these symptoms, effective ways of providing linkages to care, and ways in which standardized assessment and treatment protocols might be adapted to better suit this population.