OBJECTIVE: This study examined the association of depression severity and drug injection HIV risk behavior among injection drug users. METHOD: Injection drug users who met the DSM-IV criteria for major depressive disorder, dysthymia, or substance-induced mood disorder lasting at least 3 months were asked how often they used "needles or syringes that someone else had used" (injection risk behavior) in the past 90 days. Depression severity was measured by using the Modified Hamilton Rating Scale for Depression. RESULTS: Of the 109 subjects, 63% were male, 82% were Caucasian, and 10% were HIV positive. The subjects’ mean modified Hamilton depression scale score was 21.0 (SD=3.9). The mean number of reported instances of injection risk behavior (needle sharing) in the past 90 days was 57.5 (SD=134.7). In a logistic regression analysis in which the effects of age, race, gender, number of days on which injection drugs were used (injection days), and average number of injections per injection day were controlled, depression severity was associated with injection risk (odds ratio=1.5; 95% confidence interval=1.1–2.3). CONCLUSIONS: Greater severity of depression is associated with greater frequency of injection risk behavior among depressed injection drug users. Risk reduction programs that target depressed injection drug users need to be designed.