Summary The epidemiology in 93 proved rhinovirus infections caused by 46 different serotypes among 7 different child or adult population groups studied during 3 successive respiratory disease seasons is described. Multiple serotypes were found to circulate simultaneously in the populations and sero-types tended to disappear and not to be represented in successive seasons. Essentially all patients with rhinovirus infection responded serologically. This response was extremely homotypic and appeared to persist, though in diminished amount, for at least 4 years. The low proportion of cases of common cold yielding a rhinovirus suggests either that the diagnostic efficiency of the virus isolation method is poor or that as yet undiscovered viruses may be responsible for the marjority of such illnesses or perhaps both situations prevail. About ½ of children with rhinovirus infection in the present study displayed lower respiratory tract involvement and their illness was diagnosed as croup, bronchitis, bronchiolitis or bronchopneumonia. Little hope is held for development of rhinovirus vaccines containing a sufficient spectrum of serotypes; vaccine development must await clarification of epidemiology and must rest on future guidelines. We are indebted to Drs. S. M. Hoch, W. Freeborn, H. H. Palmer, of Merck and Co. and to Drs. C. M. Reilly, P. Schrode, L. McClelland, K. C. Christie, P. J. Koblenzer, and D. J. Bartels of University of Pennsylvania who assisted in clinical observations and in collection of specimens. B. Baron Keech, D. M. Blaney, G. Devers and P. A. Gosnell provided technical assistance.