To examine the putative protective effect of disinfectant use on HIV seroconversion among intravenous drug users, we conducted a nested case-control study comparing 22 black heterosexual HIV seroconverters with 95 persistent seronegatives matched on gender, use of cocaine, date of study entry, and duration of follow-up. For intravenous drug users who reported using disinfectant all the time, the odds of seroconversion was 0.77 (95% CI: 0.25-2.38) compared with those who reported no use of disinfectants; for those who used disinfectants some of the time, the corresponding odds ratio was 0.91 (95% CI: 0.26-3.31). The odds ratio for use of disinfectant all the time was 0.63 (95% CI: 0.10-3.91) for those injecting at galleries and 1.08 (95% CI: 0.35-3.11) for those not injecting at galleries. These data suggest a limited protective effect of disinfectant use in the field which may be more beneficial to those injecting in shooting galleries.