The antigenic relationship of 181 feline calicivirus (FCV) isolates from the United States (USA) and United Kingdom (UK) to 5 reference viruses, representing 2 vaccine strains (F9 VacNor, 2280) and 3 field strains (H, J, TN) was determined by a neutralization assay using two standardized dilutions of reference sera. A comparison between USA and UK isolates indicated that significantly fewer UK isolates could be neutralized by sera specific for each of the reference strains. Isolates from the USA were also analyzed based on the time period and geographical location from which they were derived. Analysis of the cross-neutralization results for isolates derived from the USA indicated that no single reference strain was predominant in all the geographical locations, however, antisera specific to strains 2280, H and J neutralized the highest number of isolates overall. Analysis of the neutralization patterns based on the time period from which the isolates were derived indicated that F9 VacNor was antigenically similar to 86% of feline caliciviruses isolated in 1958-1979. This number decreased to 43% for isolates derived in 1980-1995. By contrast, the J strain maintained its antigenic relatedness to approximately 75% of representative FCV isolates circulating during the last 40 years.