The aims of the present study are to establish the subacute sclerosing panencephalitis (SSPE) incidence in Bulgaria for the 25-year period 1978-2002; to analyze the SSPE incidence prior to, and in the period of, routine measles immunization; and, to analyze the clinical characteristics of SSPE. SSPE was diagnosed in a total of 40 children; 28 of were diagnosed between 1978 and 1984, and 12 between 1995 and 2002. Thirty-eight cases (95%) were non-immunized and have had an early measles infection (mean age 16 months). The SSPE onset occurred primarily between 8 and 11 years of age (52.5%) with a mean latent period of about 7 years after the measles infection. After the 10-year disease-free period (1985-1994), the SSPE incidence increased between 1995 and 2002 because of the 1991-1992 measles epidemic. During the period 1995-2002 children with earlier measles infection and earlier SSPE onset predominated, compared to the period 1978-1984. The initial clinical manifestations included intellectual deterioration in 35%, extrapyramidal hyperkinesias in 29%, epileptic seizures in 15%, hemiparesis in 10%, and visual disturbances in 10% of the cases. Nine children (22.5%) demonstrated an atypical onset. A rapidly progressive course was observed in 4 children (10%) and a chronic progressive course with pseudoremissions over 2 years-in 8 cases (20%). Our analysis of the SSPE incidence in Bulgaria for the 25-year period (1978-2002) supports the importance of early measles infection as a crucial risk factor for this persistent neuroinfection. Moreover, it confirms the role of routine measles immunization in SSPE prevention.