Cryptococcal infection uncommonly presents with pulmonary manifestations an
d even more rarely so as massive bilateral effusions. Pleural involvement i
s usually associated with underlying pulmonary parenchymal lesions and is u
nusual while on antifungal therapy. We report a patient with cryptococcal m
eningitis who, while on intravenous 5-flucytosine and amphotericin B, devel
oped life-threatening bilateral massive pleural effusions with evidence of
spontaneous resolution, consistent with prior hypothesis of antigenic stimu
lation as the cause of pleural involvement.