Noroviruses are the most common cause of outbreaks of viral gastroenteritis worldwide. Norovirus outbreaks were surveyed in Catalonia and the region of Valencia (Eastern Spain) between January 2001 and December 2006 as part of the European Union funded network "Food-borne viruses in Europe". During this time the etiology and epidemiological features of 194 outbreaks of acute non-bacterial gastroenteritis were investigated and norovirus was identified as causing 169 (87.1%) of them. Molecular epidemiology of viral strains was studied by RT-PCR and sequencing part of the RNA polymerase gene in ORF1 from 153 outbreak strains. The most commonly identified norovirus genotype was GII.4 (71.9% of the characterized outbreak strains), which is also the predominant genotype worldwide. During this survey five genetic variants of GII.4 genotype have been sequentially detected and identified as 1996, 2002, 2004, 2006a, and 2006b variants. The transition from one variant to a new one always took place over a short period of time, and thereafter the replacement of strains circulating previously was observed. These new GII.4 variants may have arisen as a consequence of viral evasion from the host immune responses, although apparently there is a lack of long-term immunity after norovirus infections.