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Human infection with Histoplasma capsulatum runs the gamut from asymptomatic to disseminated disease. CT-directed fine-needle aspiration of bilaterally enlarged adrenal glands has been used in diagnosing serious infections with this ubiquitous organism. Three cases have previously been reported in which H. capsulatum infection caused unilateral adrenal enlargement; this enlargement was diagnosed post-mortem. We describe three patients with unilateral adrenal enlargement due to H. capsulatum whose conditions were diagnosed antemortem. We encourage clinicians to include infection with H. capsulatum as well as other granulomatous diseases and tumors in the differential diagnosis of unilateral adrenal enlargement.