To determine how the injecting behaviors of injection drug users (IDUs) change over time in the context of the epidemic of acquired immunodeficiency syndrome (AIDS) and what factors may be associated with such changes, a cohort of IDUs (n = 313) initially in treatment provided structured interviews regarding drug injecting behaviors. Repeat interviews in 18 months assessed behavior change in subjects who could be contacted for follow-up (n = 220, 70.3%). The study occurred in a state where sterile syringes can be purchased without prescription in drug stores. Injection drug use occurred for 180 (81.8%) of the 220 subjects in the 12 months prior to the initial interview but in only 121 (55.0%) in the 10 months prior to the follow-up interview (p < 0.0001). Similarly, sharing of equipment decreased from 63.1% to 31.8% (p < 0.0001). Sharing with multiple partners declined from 41.9% to 10.6% (p < 0.0001). Factors associated with ongoing risk included use of injected and non-injected psychoactive substances, less time in drug dependence treatment during follow-up interval, having a sexual partner who was an IDU and not using a drug store as the primary source of syringes. Factors associated with multiple-partner sharing included use of psychoactive substances, younger age and nonwhite race.