Endemic and epidemic viral gastroenteritis are major causes of morbidity worldwide and are frequently a major cause of death in the developing world. Rotavirus, adenovirus, calicivirus, astrovirus, and the Norwalk virus family are the viruses most often associated with gastroenteritis. Of these, the major cause of epidemic viral gastroenteritis in the US is Norwalk-like viruses. Gastroenteritis caused by this virus group is responsible for such outbreaks in settings such as cruise ships, schools, camps, hospitals, day-care and extended care facilities, football games and festivals.

As early as the 1950s and 1960s electron microscopy (EM), including negative stain EM, was established as a diagnostic tool for identifying viruses. Negative stain EM is especially useful for identifying viruses that are difficult or impossible to culture (eg. viruses in the Norwalk family). The first Norwalk virus was identified in the 1969 by immune-negative stain EM. Many antigenic types were identified soon afterward that did not cross-react with the prototype Norwalk virus.