Two caliciviruses occur in Australian wild rabbits: rabbit calicivirus Australia 1 (RCV-A1) and rabbit haemorrhagic disease virus (RHDV), which is used in Australia as a biocontrol agent to reduce feral rabbit populations. There is concern that RCV-A1 acts as a natural vaccine and protects from lethal RHDV infection. To investigate this hypothesis, domestic rabbits were perorally infected with RCV-A1, monitored for 28 days and subsequently challenged with RHDV. We show that RCV-A1 causes a non-pathogenic infection and is shed in faeces for up to 7 days post-infection. RCV-A1 was detected in the bile 2 months post-inoculation, indicating a prolonged or possible persistent infection. All animals infected with RCV-A1 developed antibodies cross-reacting to RHDV. When challenged with RDHV, half of the rabbits (n=4) survived the infection. The results indicate that RCV-A1 is likely to persist in rabbit populations and can elicit partial cross-protection to lethal RHDV infection.