Limited prevalence data for HIV, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) exist for Afghanistan. We studied a cross-sectional sample of adult injection drug users (IDUs) in Kabul, Afghanistan, from June 2005 through June 2006. Study participants completed interviewer-administered questionnaires and underwent testing for HIV, antibody to HCV, and HBsAg. Overall prevalences of HIV, HCV, and HBsAg were 3.0% (95% confidence interval [CI] 1.7%-5.1%), 36.6% (95% CI 32.2%-41.0%), and 6.5% (95% CI 4.2%-8.7%), respectively (N = 464). Among male IDUs (n = 463), risky behavior, including sharing syringes (50.4%), paying women for sex (76.2%), and having sex with men or boys (28.3%), were common. Needle sharing, injecting for > or = 3 years, and receiving injections from nonmedical providers were independently associated with increased risk for HCV infection. The high prevalence of risky behavior indicate that Kabul is at risk for an HIV epidemic. Scale-up of harm-reducing interventions is urgently needed.