An epidemic of enterovirus 71 (EV71) infection compatible with hand, foot and mouth disease and associated with high morbidity and mortality occurred in Taiwan in 1998. We recruited 90 patients (50 males, 40 females) with definite EV71 infections for clinical and laboratory analysis. The neurological signs and symptoms, all of which occurred during the febrile period, in patients with central nervous system (CNS) involvement (aseptic meningitis, encephalitis or myelitis) were myoclonic jerks (23/33), vomiting (10/33), ataxia (7/33), lethargy (6/33), seizure (4/33) and tremor (2/33). Patients with CNS involvement had longer durations of fever (4.6+/-0.2 vs. 3.1+/-0.3 d; p <0.01) and a higher white blood cell count (12,512+/-658 vs. 10,607+/-409 cells/mm3; p = 0.01) than patients without CNS involvement. The case fatality rate in patients with CNS involvement was 4/33 (12%), whereas no fatalities (0/57) occurred in patients without CNS involvement. Six of 11 patients subjected to MRI showed a high intensity T2-weighted signal in the brainstem. A nested fluorescent RT-PCR for detection of virus in throat and stool specimens showed higher sensitivity than viral culture. Viremia was detectable using RT-PCR in 20% of cases (3/15), whereas no virus was isolated from culture or detected by RT-PCR in cerebrospinal fluid.