I recently consulted on a young woman who had acquired fever, profuse pulmonary shadowing, and liver function abnormalities following a 1997 visit from her residence in upstate New York to the Mississippi Valley. An open-lung biopsy at that time revealed noncaseating epithelioid granulomas (NCG) consistent with sarcoidosis; fungal elements were not evident. The treating physician initiated prednisone therapy, but after a week, a histoplasmosis complement fixation titer of 512, later supplemented by isolation of Histoplasma capsulatum organisms from the biopsy sample, led to its replacement with a short course of amphotericin B, followed by months of itraconazole therapy, with the expectation that her progressive disseminated histoplasmosis would resolve. She was unavailable for follow-up until 2001, when she was re-referred for evaluation of increasingly severe shortness of breath. Prednisone had been provided by her primary physician. A chest radiograph showed profuse pulmonary shadowing; high-resolution CT demonstrated findings characteristic of advanced stage IV sarcoidosis; pulmonary function tests revealed a severe restrictive defect accompanied by a marked reduction in diffusing capacity. Prednisone was discontinued because of the concern that her histoplasmosis had relapsed. BAL fluid was negative for histoplasma antigens and showed no stainable or culturable H capsulatum; her histoplasma complement fixation titer was zero. Her alkaline phosphatase was markedly elevated. CT of her abdomen showed numerous, homogeneously distributed microlucencies in her liver indicative of either micronodules or microabscesses. A percutaneous liver biopsy demonstrated NCG; no organisms were visible and fungal culture showed no growth. A marked progression of the abnormalities identified on her pulmonary function testing, following 1 week of prednisone omission, led to its reinstitution; itraconazole was added to prevent relapse of histoplasmosis. The physicians participating in her care concluded that, whereas previously she had chronic progressive disseminated histoplasmosis, she now had stage IV sarcoidosis.