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To compare enterovirus 71 (EV 71) with coxsackievirus A16 (Cox A16) clinical illness in patients at Chang Gung Children's Hospital during Taiwan's enterovirus epidemic of 1998.With the use of the immunofluorescence assay and neutralization test, 177 cases of EV 71 and 64 cases of Cox A16 illness were confirmed from April to September, 1998. The clinical signs and symptoms, complications and case fatality rates were compared.Three-fourths of the cases were younger than 3 years of age, and the ratio of males to females was 1.3 in the EV 71 group and 1.2 in the Cox A16 group. In the EV 71 group 120 (68%) cases were uncomplicated, including 94 cases of hand, foot and mouth disease and 15 cases of herpangina, and 57 (32%) cases had complications, including 13 (7.3%) cases of aseptic meningitis, 18 (10%) cases of encephalitis, 4 (2.3%) cases of polio-like syndrome, 8 (4.5%) cases of encephalomyelitis and 12 (6.8%) cases of fatal pulmonary edema. Fourteen (7.9%) patients died, including 12 cases of pulmonary edema and 2 cases of encephalitis; seven (4%) patients had sequelae. By contrast, 60 (94%) of the 64 cases of Cox A16 infection were uncomplicated and only 4 (6.3%) cases were complicated by aseptic meningitis; no fatalities or sequelae were observed. By multivariate analysis vomiting (P = 0.01) and fever higher than 39°C plus lasting longer than 3 days (P = 0.02) were significantly more frequent in the EV 71 group.EV 71 illness is more severe with significantly greater frequency of serious complications and fatality than is illness caused by Cox A16.