We describe the case of a 42-year-old immunocompetent man who developed severe pneumonia with Cryptococcus neoformans var. grubii following influenza A infection. With the commencement of liposomal amphotericin and flucytosine, his condition dramatically deteriorated. Secondary bacterial infection following influenza is a well-recognized phenomenon and there are increasing reports of invasive aspergillosis occurring in the critically ill; however, secondary infection with cryptococcus in the immunocompetent patient is rare. The absence of an immunological defect in our patient raises the possibility of influenza predisposing to cryptococcal infection. We hypothesize that the cause of our patient's deterioration with antifungal treatment represented either a reaction to amphotericin or a vigorous immunological response to released fungal antigen. Our experience alerts the clinician to the potential for clinical deterioration with antifungal treatment of cryptococcal pneumonia in the immunocompetent host, and raises the question of a link between influenza and cryptococcal infection.