To describe prevention activities and risk behavior in cities where human immunodeficiency virus (HIV) was introduced into the local population of injecting drug users (IDUs), but where seroprevalence has nevertheless remained low (< 5%) during at least 5 years. A literature search identified five such cities: Glasgow, Scotland; Lund, Sweden; Sydney, New South Wales, Australia; Tacoma, Wash; and Toronto, Ontario. Case histories were prepared for each city, including data on prevention activities and current levels of risk behavior among IDUs. Injecting drug users recruited from both drug treatment and non-treatment settings in each city. A variety of HIV prevention activities for IDUs had been implemented in each of the five cities. There were three common prevention components present in all five cities: (1) implementation of prevention activities when HIV seroprevalence was still low, (2) provision of sterile injection equipment, and (3) community outreach to IDUs. Moderate levels of risk behavior continued with one third or more of the IDUs reporting recent unsafe injections. In low-seroprevalence areas, it appears possible to severely limit transmission of HIV among populations of IDUs, despite continuing risk behavior among a substantial proportion of the population. Pending further studies, the common prevention components (beginning early, community outreach, and access to sterile injection equipment) should be implemented wherever populations of IDUs are at risk for rapid spread of HIV.