The objective of this study was to compare drug injection- and sex-related risk behaviors of younger and older injection drug users (IDUs) in two adjacent neighborhoods. IDUs were recruited from street settings in two adjacent neighborhoods in San Francisco in April, 1997. All participants were interviewed using a standardized questionnaire and were tested for HIV antibodies. Drug injection- and sex-related risk behaviors were compared between younger IDUs (< 30 years; n = 56) and older IDUs (> or = 30 years; n = 116). Younger IDUs were more likely to be white, be homeless, have injected amphetamines, and have been arrested in the past year. Older IDUs were more likely to be African American and smoke crack cocaine; they had injected a mean of 18 years longer. Younger IDUs were more likely to have shared syringes in the past month (52% versus 10%; p < .05), report drug overdose in the past 15 months (39% versus 7%; p < .05), and to have had unprotected vaginal intercourse in the past 6 months (77% versus 53%; p < .05). After controlling for confounding factors using logistic regression analysis, all these associations remained significant. There is an urgent need for innovative prevention programs that target younger, homeless IDUs.