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Aim. To analyse overall and cause-specific mortality among problem drug users (PDUs) attending treatment centres in Rome and to evaluate differences in mortality between genders. Methods. A cohort of 11 432 PDUs entering treatment in Rome between 1980 and 1995 was enrolled and followed-up as of May 31, 1997. Directly standardized mortality rates and standardized mortality ratios (SMRs) and their 95% confidence intervals (95% CI) were calculated. Results. The study population included mainly males (82%), heroin users (92%) and had a mean age of 26.6 (SD 5.9) at enrolment. At the end of the study period 1734 deaths were observed. Overall mortality rates began to increase in 1985-86 and decreased slightly afterwards. AIDS mortality peaked in 1991-92 (13.2/1000) and fell in the following years. A slight decrease in overdose mortality also occurred after 1989-90. Mortality for causes other than AIDS and overdose remained high and relatively steady for the whole study period. Women showed higher mortality rates for AIDS but lower mortality rates for overdose than males. Overall mortality risk among drug addicts was about 15 times higher compared to the general population of the same age among men, and 38 times higher among women. Conclusions. AIDS mortality among drug addicts began to decrease earlier than expected; the decrease was particularly significant in the period 1993-94 for both sexes. Afterwards a continuous but slight decrease was observed among males only. Even though overdose mortality has also decreased slightly in recent years, we still observe high mortality levels for both overdose and all other causes. These findings suggest that interventions directed specifically towards the reduction of baseline mortality are still needed.