Norwalk virus is a major cause of epidemic acute and mild gastroenteritis, or diarrhea, in older children and adults. The first recorded epidemic attributed to Norwalk virus occured in an elementary school in Norwalk, Ohio, in 1968. Bacteria-free fecal filtrates derived from adult patients were fed to volunteers. These volunteers consequently became ill and provided evidence that gastroenteritis could be induced with a nonbacterial agent. In 1972, NV was first seen using Immuno-EM. By 1990, molecular cloning was allowing detailed sequence and expression of the capsid protein. The first 3-dimensional reconstruction of NV capsid was accomplished in 1994, using cryo-EM techniques, at 22 angstroms resolution. Presently, in 1996, we are in the process of determining the structure of NV at 3 angstroms resolution using X-ray crystallography, to reveal detailed information on the folding of capsid protein.