To estimate the excess mortality of injecting drug users (IDU) stratified by HIV serostatus compared with the general population in Italy. To compare total and cause-specific mortality in HIV-positive versus HIV-negative IDU, in order to identify possible HIV-related non-AIDS causes of death in this population. All IDU attending two drug-treatment centres in Rome who underwent HIV testing between 1985 and 1991 were enrolled into a prospective study. The end-point of the study was death from any cause by 31 December 1991. Mortality rates were compared using age-adjusted standardized mortality ratios and person-time techniques. Of the 2431 IDU, 1661 (68.3%) were HIV-seronegative and 82 seroconverted. Of 181 deaths, comprising 89 from AIDS and 92 from other causes, the mortality rate was 4.5 and 0.8 per 100 person-years in HIV-seropositives and HIV-seronegatives, respectively. For non-AIDS mortality in HIV-seropositives, the overall rate was 1.7 per 100 person-years. Deaths from overdose and endocarditis/embolus tended to be higher in HIV-seropositive than HIV-seronegative IDU, although there was no difference in the rate of deaths due to pneumonia by HIV serostatus. These data are consistent with other studies demonstrating a higher frequency of mortality among HIV-seropositive IDU. The excess in overdose mortality among HIV-seropositives is disturbing and merits further investigation.