The objective of this study was to characterize longitudinal patterns of drug injection behavior for individuals and to identify their early determinants. Participants were 1,339 injection drug users recruited into the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, through community outreach efforts. The study was initiated in 1988, and follow-up continued through 2000, with semiannual visits. Patterns of self-reported drug injection (yes/no) were defined for each participant, based on the number of drug-use transitions. The effect of baseline factors was assessed using multinomial logistic regression models. Over the 12-year study period, four patterns were noted: 29% of participants remained persistent drug injectors, 20% ceased injection, 14% relapsed once, and 37% had multiple transitions. Persistent injectors had the shortest follow-up and the highest mortality. For persons who changed their behavior, 3.4 years elapsed before their first cessation attempt, on average. Factors differentiating the groups included history of incarceration, young age, participation in drug treatment programs, recent overdose, and commercial sex. The observed long-term injection patterns are consistent with the view of drug addiction as a chronic disease. This view emphasizes the need for prolonged efforts to sustain cessation and to prevent adverse health and social outcomes among injection drug users.