This investigation reports the prevalence and clinical profile of subacute sclerosing panencephalitis in two developed cities of southern China. A territory-wide survey was conducted to identify all subacute sclerosing panencephalitis cases diagnosed during 1988-2002 in Hong Kong and Macau. Altogether, 10 cases (male:female = 7:3) were identified of whom six were still alive. The prevalence rate of subacute sclerosing panencephalitis in Hong Kong and Macau in 2002 was 1 per million total population or 5.5 per million children. The mean age of presentation was 9.4 years (range = 4-14 years). Presenting features included myoclonus (60%), deterioration in school performance (30%), and transient visual impairment (10%). The clinical course was highly variable. Most had subacute course, but two deteriorated rapidly and died within 6 months. Seven children had measles infection, and the majority of infection (86%) occurred during the world measles epidemic in 1988. The mean interval between measles infection and onset of subacute sclerosing panencephalitis was 6.5 years (range = 3-11 years). There has been an increasing trend of subacute sclerosing panencephalitis in southern China after the measles outbreak in 1988. Active surveillance of subacute sclerosing panencephalitis for those with measles infection during the 1988 outbreak is necessary to conduct multicenter drug trials for this devastating disease.