The relationship between the infectivity of the feline calicivirus (FCV) vaccine strain F-9 and capsid destruction (virolysis) in response to available chlorine was investigated under standardized light soil disinfection conditions. Virolysis was measured using RNase pretreatment (in order to destroy exposed RNA following chlorine treatment) and quantitative reverse transcription PCR. A comparison between the results of plaque assays and virolysis following exposure of FCV F-9 grown in tissue culture to different concentrations of available chlorine showed a similar log-linear relationship, with >4-log reductions occurring at 48 and 66 ppm, respectively. Three non-epidemiologically linked human GII.4 noroviruses (NoVs) present in dilute clinical samples showed behavior similar to each other and were 10 times more resistant to virolysis than cultured FCV F-9. FCV F-9 when present in dilute human GII.4 samples acquired increased resistance to virolysis approaching that of human NoVs. This study represents a direct comparison between the virolysis of a surrogate virus (FCV F-9) and that of human GII.4 NoVs within the same matrix in response to available chlorine. The results support the view that matrix effects have a significant effect on virus survival.