A 41-year-old man presented with night sweats, fever, and substernal chest pain approximately 5 months after being treated for community-acquired pneumonia. Chest radiograph revealed a mediastinal mass that was confirmed by computed tomography (CT) of the thorax. During surgery, enlarged paratracheal lymph nodes and a mass surrounding the right lower lobe bronchus and bronchus intermedius were found. Multiple biopsies from the mass showed that it consisted mainly of acellular fibrous tissue, but a small number of fungal forms typical ofHistoplasma capsulatumwere seen at the edge of the fibrotic reaction. The lymph nodes contained granulomatous inflammation and areas of necrosis, but no organisms were identified. The patient was treated with fluconazole for 6 weeks with resolution of symptoms. After completion of therapy, a follow-up CT scan of the thorax showed involution of the mediastinal mass. There has been no recurrence of symptoms or radiographic abnormalities for 24 months since cessation of fluconazole. This case illustrates isolated mediastinal involvement by histoplasmosis and suggests that therapy with fluconazole at this stage may prevent the often devastating late complications of mediastinal fibrosis.