This study assessed relationships between residual risk behavior (risk behavior among persons participating in effective HIV prevention programs) and HIV infection. Structured interviews and HIV tests were obtained from participants in six large U.S. syringe exchange programs. Program characteristics were obtained through interviews with the directors. Findings indicated that injection risk behaviors varied significantly across the six programs--from 10% to 27% of the participants at each program reported receptive sharing of needles and syringes in the 30 days prior to the interview. HIV prevalence ranged from 2.5% to 22.2% across the six programs. HIV prevalence among new injectors was strongly related to HIV prevalence among long-term injectors across the programs (r = .869). There was a consistent pattern of negative relationships between injection risk behaviors and HIV infection across the six programs (higher rates of risk behavior at a program associated with lower HIV infection). As a result, appropriate evaluation of HIV prevention programs may require not only information on continuing risk behavior and HIV infection among program participants but also historical information on the epidemiology of HIV in the local community.