To examine the putative protective effect of disinfectant use on HIV seroconversion among injecting drug users, we conducted a nested case-control study of black heterosexuals comparing 34 HIV seroconverters with 154 persistent seronegatives matched on gender, cocaine injection (yes/no), date of study entry, and duration of follow-up. Injecting drug users who reported using disinfectant all the time had an odds ratio of seroconversion of 0.87, as compared with those who reported no use of disinfectants; the corresponding odds ratio was 1.00 for those who used disinfectants less than all the time. We examined the effect of drug use and sex practice variables, and responses to a socially desirable responding scale as possible confounders for the effect of needle disinfection on HIV seroconversion; the adjusted odds ratios for disinfectant use and HIV seroconversion were unchanged in this analysis. Despite limited statistical power and the potential for residual confounding, these data suggest that disinfection of injection equipment is not a substitute for abstinence from drugs or use of sterile injection equipment.