During April-July 1998, the Ministry of Health in Taiwan received approximately 90,000 reports of hand, foot, and mouth disease (HFMD) among young children based on passive surveillance from sentinel physicians. Approximately 320 children have been hospitalized with HFMD associated with suspected meningitis, encephalitis, or acute flaccid paralysis (AFP), and at least 55 have died. This report describes the clinical course of two fatal cases and presents summary findings from an ongoing clinical, epidemiologic, and laboratory investigation of the 55 deaths.