Enterovirus 71 (EV71) has emerged as a significant pathogen with potential to cause large outbreaks. Because little is known about its seroprevalence and molecular epidemiology in Germany, data for 1997-2007 are presented. Four hundred thirty-six sera from persons aging 10 months to 75 years were tested in a neutralisation test; 63.4% of pre-school children were seronegative, whereas about 75% of adults had antibodies to EV71. Phylogenetic analysis of 28 isolates associated with neurological or cutaneous manifestations showed that isolates belonging to genogroup C1 predominated in 2000-2005, followed by a change to genogroup C2 in 2006 and 2007. This shows the importance of monitoring the diversity of one of the most relevant neurotropic enteroviruses.