Hand-Foot-and-Mouth Disease (HFMD) is a mild exanthematous illness seen worldwide, affecting mainly children under ten years of age. The causative agents were initially Coxsackie virus type A 16 and related serotypes. The situation changed drastically about thirty years ago with the advent of a new aetiological agent, Enterovirus type 71 (EV 71), which has caused very large outbreaks with severe complications and many deaths.The authors report an outbreak of papulovesicular lesions on the skin and oral mucosa compatible with the diagnosis of HFMD in children in and around Calicut in October 2003. Clinical and laboratory study in collaboration with the National Institute of Communicable Diseases, Delhi. Eighty one children with the syndrome were examined and followed up from October 2003 to February 2004, when the outbreak subsided.The outbreak was mild and all children recovered within 1 to 2 weeks.Acute and convalescent paired serum samples collected from 19 patients were examined at the NICD for IgM antibody against EV 71 by microneutralisation test in cell culture. All the paired samples tested showed significant rise in titre of antibodies, confirming the diagnosis of EV 71 infection in each of them.