The evolution of our understanding of immunity to calicivirus infection, using Norwalk virus as the prototype, is discussed in three stages: (1) "ancient times (1972-1978), when human volunteer studies prevailed, (2) the "middle ages (1978-1990), which were characterized by the development and implementation of solid-phase immunoassays based on native viral antigens, and (3) "modern times (1990 to present), which began with the cloning of the genome of the noncultivatable 8FIIa strain of Norwalk virus and resulted in a readily available source of recombinant virus-like particles that have revolutionized the study of caliciviruses. Throughout these stages, it has been shown repeatedly that short-term immunity develops to homologous virus. However, the search for determinants of long-term immunity continues. These studies will likely be facilitated by the newest reagents-the noninfectious recombinant virus-like particles-used in the setting of human volunteer studies and large epidemiologic studies.