An unusual illness of children characterized in a typical case by slight malaise, fever, and discrete vesicular lesions in the mouth and on the hands and feet, occurred in many areas of California and possibly other western states, during the summer of 1959. In 33 cases observed in this study, the oral lesions resembled those of herpangina, but the syndrome was distinguishable from herpangina by the frequent presence of lesions on the buccal mucosa and tongue and also, in 8 cases, by the presence of a maculovesicular exanthem. Evidence of infection with a Coxsackie virus, group A, type 16, was found in 11 of 15 cases in which viral studies were done. This syndrome is not known to have been recorded previously in the United States, but a localized outbreak of a similar disease, likewise attributed to Coxsackie A16 virus, occurred in Toronto, Canada, in 1957.