Although injection drug users have been shown to reduce high-risk injection behaviors in response to the epidemic of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the total elimination of risk behaviors has not been achieved. A more fundamental preventive measure may be to keep drug users from starting to inject at all. The authors selected 184 drug users from a cohort study in Amsterdam, the Netherlands, from 1985 to 1992, who had reported at entry to the study that they either had never injected drugs or had injected for the last time more than 1 year before the initial visit. Over a 5-year follow-up period, impressively high cumulative rates of transition to injection drug use were found in both groups. Among drug users who had never injected drugs, 30% began injecting; among those who had injected drugs 1-5 years before their entry into the study, 70% started injecting again. These rates were stable over time. The authors also confirmed that new injectors are at high risk of acquisition of HIV infection. With the use of a survival and a nested case-control analysis, the following independent risk factors that increased the likelihood of starting to inject were found: previous injecting history, ethnicity other than Surinamese/Antillean, regular long-term use of cocaine, current use of heroin, and a current steady sexual relationship with a partner who injects drugs. Given the high and stable incidence of initiation of injection among drug users within the cohort study, the prevention of this behavior appears to be difficult. Additional studies are needed to determine effective prevention strategies.