Analysis of the National Hospital Discharge Survey data for 1988-1997 revealed a substantial disease burden associated with encephalitis in the United States: on average, there were nearly 19,000 hospitalizations (7.3 hospitalizations per 100,000 population), 230,000 hospital days, and 1400 deaths annually. For most encephalitis-associated hospitalizations (59.5%), the etiologic agent was unknown or not recorded; the most common etiologic categories among known causes were "viral" (38.2%) and "other infectious" (34.1%). The most common individual diagnoses with known agents were herpetic and toxoplasmic encephalitides (each associated with an annual average of 2100 hospitalizations). Human immunodeficiency virus infection was listed among discharge diagnoses for 15.6% of hospitalizations. Rates of encephalitis-associated hospitalization were highest for children <1 year old and persons > or =65 years old. The etiology of encephalitis was unknown for persons > or =65 years old significantly more often than it was for younger persons. The average cost of an encephalitis-associated hospitalization, as determined by the Healthcare Cost and Utilization Project for 1997, was $28,151, for an annual national cost of hospitalization of $650 million.