OBJECTIVE:To examine the evolution of dementia in HIV-positive injecting drug users (IDU) in Edinburgh. DESIGN:Case-control study. PARTICIPANTS:Twenty six (6%) out of 404 patients in the Edinburgh cohort of HIV-positive IDU who have developed HIV-1-associated dementia in the 10 years since infection and seroconversion. METHODS:Patients were tested repeatedly, where possible, on a range of neuropsychological and neurophysiological measures. The results from patients with dementia were compared with those of age, sex and IQ-matched non-demented HIV-positive controls from the cohort. An auditory event-related potential (P3 or P300), a neurophysiological measure of cognitive function, detected the onset of a marked slowing of cognitive and psychomotor functions. Neuropsychological measures that involve the speed of information processing such as the Trail-Making task also identified the early stages of dementia. RESULTS:Dementia was associated with a more advanced stage of systemic disease, increased rates of decline in CD4 cell counts and markedly reduced survival compared with the non-demented controls. No evidence for a protective effect of treatment with zidovudine was detected. CONCLUSION:In the first 10 years after infection with HIV-1 dementia is an individual development, not the clinical extreme of general intellectual impairment, and had occurred in at least 6% of our IDU cohort. Future questions concern the long-term rate of dementia, the critical neuropathological change and the true potential for early treatment.