Background:In syringe-mediated drug-sharing (backloading), injecting drug users (IDU) use their syringes to mix drugs and to give measured shares to other IDU by squirting drug solution into the syringes of other IDU. Backloading has been discussed as a potential HIV risk factor, but its role as an HIV transmission route has not been established empirically. Methods:Six hundred and sixty IDU who had injected drugs in the previous 2 years were street-recruited from Bushwick, New York City through chain referral, tested for HIV antibody and interviewed about sexual and drug-risk behaviors. Results:Receiving drugs via backloading in the previous 2 years was reported by 24.5% of the subjects. These subjects had significantly higher HIV seroprevalence than those who did not receive drugs by backloading (odds ratio, 2.2; 95% confidence interval, 1.5–3.1). Backloading remained positively and significantly associated with HIV seropositivity in stepwise logistic regression, and in a series of simultaneous logistic models controlling for sociodemographic variables and for sexual and drug risk variables. Conclusions:Backloading can be a route of HIV transmission among IDU and should be incorporated into risk-factor studies and HIV transmission modeling. Many IDU who avoid other high-risk drug-injection practices may overlook the risk of backloading. HIV prevention programs should warn IDU against syringe-mediated drug-sharing and work together to develop ways to avoid it. AIDS 1993, 7:1653–1660