We studied fungemia over time in outbred mice infected with Cryptococcus ne
oformans and looked at its relationship with the intravenous (i.v,) inoculu
m size, tissue burden and survival. Fungemia was evaluated by culture of 10
mu l of peripheral blood from living mice or by culture of buffy coats fro
m sacrificed animals. For all inoculum sizes studied, fungemia could last s
everal weeks after the i.v. inoculation. Individual susceptibility of outbr
ed mice to cryptococcal infection was evidenced by variations in the course
, duration and magnitude of fungemia and tissue localizations. These result
s suggest that the fungus can recirculate after the initial i.v. inoculatio
n. Fungemia, assessed by culture of buffy coats, correlated with the extent
of infection in the spleen, lung or brain (P < 0.001) on day I after inocu
lation but only with yeast burden in lung or spleen on day 8, thus demonstr
ating that brain reacts differently to C. neoformans infection than other o
rgans. Comparison of blood culture techniques and examination of smears sug
gest that cryptococci might circulate within leucocytes. Finally, quantitat
ive blood cultures may accurately assess the fungal load during experimenta
l cryptococcosis.