The electrophoretic karyotypes of 32 clinical and 3 environmental Cryp
tococcus neoformans isolates from New York City were studied by contou
r clamped homogeneous electrophoresis. There was extensive variation a
mong the electrophoretic karyotypes of isolates from different patient
s. Sequential C. neoformans isolates from patients with chronic or rel
apsing infection had very similar karyotypes. However, minor differenc
es in electrophoretic karyotypes were detected among sequential isolat
es from 50% of the patients studied, suggesting the occurrence of chro
mosomal rearrangements or deletions in vivo, This hypothesis was teste
d by infecting mice, recovering isolates from mouse organs, and compar
ing the electrophoretic karyotypes before and after passage, Three cli
nical and three environmental strains were studied before and after pa
ssage in mice. Karyotype differences were detected after mouse passage
for one clinical and two environmental strains, Our results indicate
(i) extensive karyotype variation among isolates from a small geograph
ic region, (ii) a high frequency of electrophoretic karyotype differen
ces among sequential isolates from individual patients, and (iii) the
occurrence of electrophoretic karyotype changes during experimental in
fection of mice, The implications of these observations are discussed.