Most examples of pulmonary histoplasmosis, including histoplasmoma and chronic histoplasmosis, are characterized by typical necrotizing granulomatous inflammation. Only disseminated histoplasmosis is recognized as causing a different reaction which consists of ingestion of organisms by macrophages without granuloma formation. The histologic features of acute pulmonary histoplasmosis are not well described as this form of the disease is rarely biopsied. We report the biopsy findings in 4 cases of acute pulmonary histoplasmosis, which seem to be unique to this form of Histoplasma infection. There were 3 men and 1 woman who ranged in age from 40 to 68 years. All presented acutely with fever and other flu-like symptoms. Radiographically, a solitary nodular infiltrate was present in 3 and bilateral reticulonodular infiltrates in one. Histologically, all 4 biopsies showed a nodular parenchymal inflammatory infiltrate composed of lymphocytes and histiocytes filling alveolar spaces and expanding the adjacent interstitium. Areas of parenchymal necrosis were additionally present in 3 cases. Vasculitis composed of lymphocytes and histiocytes was present in all, and was striking in 3, resulting in a resemblance to grade 1 lymphomatoid granulomatosis (LYG). Tip-offs to the correct diagnosis were small necrotizing granulomas scattered within the lymphohistiocytic infiltrate (3 cases), scattered histiocyte aggregates, and a few multinucleated giant cells. The diagnosis was confirmed in all by the presence of Histoplasma yeasts in Grocott methenamine silver-stained slides. Acute pulmonary histoplasmosis may cause a lymphohistiocytic infiltrate with necrosis and vasculitis that is suggestive of LYG. This observation emphasizes the importance of examining special stains for organisms before diagnosing grade 1 LYG.