The impact of depression on drug users is extensive, serving as a trigger for high-risk injection practices and continued drug use. Yet the ability to retain active drug users in mental health treatment has never been tested clinically. We recruited injection drug users (IDU) for a randomized study of combined psychotherapy and pharmacotherapy for the treatment of depression. Among the 53 SCID-diagnosed depressed subjects assigned to the combined treatment group, 43.4% were "fully adherent" to treatment (75% or greater attendance at cognitive-behavioral therapy (CBT) sessions or 75% or greater adherence to the pharmacotherapy regimen). The correlation of CBT attendance and pharmacotherapy use was high (r(s) =.74). Persons with double depression (major depression plus dysthymia) were most likely to be fully adherent (p =.01); frequency of heroin use was inversely associated with adherence. Developing public health treatment interventions to engage out-of-treatment, dually-diagnosed IDUs is possible.