When the albino (laboratory) mouse was found to be useful for the prod
uction of high titering reagents, improvements in diagnostic methods s
oon followed. DalIdorf, Bugher, Casals, Lennette, Koprowski, Theiler,
and Webster each made contributions that were central to the generatio
n of assays allowing much more precise measurements of virus than had
been possible. With the discovery of hemagglutination by Hirst and its
application to both hemagglutination-inhibition tests for antibody to
viruses and the study of virus-cell attachment mechanisms, a relative
ly simple and inexpensive tool became available. Subsequent efforts by
Sabin and Buescher and by Clarke and Casals applied this method as we
ll as complement-fixation and neutralization to epidemiological and la
boratory studies of arboviruses and arboviral diseases. Worldwide stud
ies of arboviruses, supported by the Rockefeller Foundation? led to th
e discovery of newly recognized viruses and their geographic distribut
ions. Later, electron microscopic studies by Holmes and Murphy corrobo
rated the antigenic studies of Casals, Shope, and others and the casca
de of information regarding the molecular characteristics and genomic
sequences of viruses subsequently provided powerful other analytical t
ools. In 1993 a previously unrecognized hantavirus, Sin Nombre virus,
was shown to be the etiologic agent of Hantavirus Pulmonary Syndrome i
n the U.S., and various techniques were used to determine the epidemio
logy and natural history of this virus. Longitudinal studies of hantav
iruses in the southwestern U.S. are yielding information useful for un
derstanding the fundamentals of transseasonal transmission, epizoology
, epidemiology, evolution, epidemic potential, prevention, and control
of hantaviruses, here and elsewhere. Mice of various species, sizes,
shapes, and colors have been central, if involuntary, participants in
these hantavirus studies and advances. We have, in a way, come full ci
rcle.