Objective To investigate the relation between HIV-induced brain lesions, zidovudine (ZDV) treatment and survival length in a well-defined population of HIV-positive patients. Methods and patients Ullevål Hospital has the responsibility for treating all AIDS patients from the city of Oslo except haemophiliac patients. The patient population in this autopsy study comprised all adult AIDS patients in Oslo who were treated at our hospital and died during 1983–1994 (n = 171). This represents 86% of all adult AIDS patients from Oslo who died during the same period. Full autopsy, including neuropathological examination of the brain and spinal cord, was performed on 128 (75%) of those who died. Results No significant differences were found between autopsy and non-autopsy cases with regard to sex, age, risk groups, survival length or ZDV treatment. In the autopsy material, multinucleated giant cells (MGC) in brain tissue were found in 29 cases and diffuse damage of white matter in 52 cases. Analysis shows that ZDV (600 mg per day) reduced the incidence of these brain lesions, but only if continued until death. A second finding was an increased incidence of HIV-induced brain lesions for those with long-term survival. Together these observations may explain a substantial part of the time-trend in the incidence of MGC in Oslo. MGC were frequent (40%) during the first years of the epidemic, although survival length was short in this period. The incidence fell markedly around the time ZDV was introduced and later remained low in those using ZDV until death. The incidence of MGC has, however, increased during the later years, the new cases mainly occurring in patients who had discontinued ZDV use. Conclusion If continued until death, ZDV can reduce the incidence of HIV-induced brain lesions in AIDS patients. When ZDV treatment is terminated a rapid increase occurs in the incidence of HIV encephalitis.