In this study, we examined the relationship between depressive symptoms and needle-sharing behavior in a community sample of intravenous drug users (N = 499) in Baltimore, Maryland. Based on the polytomous logistic regression, higher depressive symptoms were positively associated both with needle sharing after cleaning with bleach and with needle sharing without first cleaning with bleach at the bivariate analyses. This relationship remained significant (OR = 1.66) even after adjusting for demographic characteristics, life events, drug use patterns, and social and drug networks. A significant synergistic effect of depressive symptoms and drug network on needle sharing after cleaning with bleach and needle sharing without cleaning was observed. More depressed intravenous drug users who also had a larger drug network were found to be at higher risk of needle sharing after cleaning with bleach, as well as needle sharing without cleaning (OR = 2.59). Depression status is discussed as a predisposing factor and drug network size as a precipitating factor for needle-sharing behavior. Implications for preventing needle-sharing behavior by reducing depressive symptoms are discussed.