To study the prevalence of HIV and infections with related transmission patterns, we interviewed and obtained blood samples from 220 injecting drug users (IDUs), sampled by snowballing, from the city of Santos in the state of São Paulo, Brazil, where the estimated number of IDUs (10,000) comprises approximately 2% of the entire population. Seroprevalence of HIV, hepatitis B and C, syphilis, and HTLV (1 and 2) was assessed and compared with that in 197 blood donors from the same city, matched for age and gender. Risk behavior related to HIV was assessed by a standard questionnaire applied to the IDU sample. Univariate and multivariate analyses of the risk factors were performed. Seroprevalences found were 62% for HIV, 75% for HCV, 75% for HBV, 34% for syphilis, and 25% for HTLV (1 and 2) among IDUs, which compare with 0.0%, 2%, 23%, 12%, and 1% for blood donors, respectively. The risk for parenterally transmitted infections in this IDU community was higher than that for sexually transmitted infections (odds ratio for syphilis, 3.57; hepatitis B, 10.0; and hepatitis C, 100). The results of the mutivariate risk analysis showed that daily rate of ID use >5 times/day (OR = 6.73), not changing behavior to avoid AIDS (OR= 3.28), ID use >15 days/month (OR = 2.72), and ID use in the last 2 months (OR = 2.23) were the risk behaviors significantly associated with HIV infection.