Four culture-documented cases of pulmonary sporotrichosis, three primary infections and one with multisystem involvement, are presented. Two of these patients are the first reported cases of primary lung disease treated with ketoconazole. This antifungal agent appears to be ineffective in eradicating this infection. The four cases, as well as a review of the literature, illustrate several important aspects of this rare disease. Pulmonary sporotrichosis is most commonly found in males with a history of alcohol abuse who are between the ages of 30 and 60. The infection is usually confined to the parenchyma of the lung but can involve hilar and mediastinal lymph nodes, pleura, skin, subcutaneous tissue, and joints. All but two cases have been reported in the United States, and the majority reside within states bordering the Missouri or Mississippi rivers. Direct occupational or environmental exposure appears to be an important predisposing risk factor. The onset of the disease is insidious, presenting in a manner similar to many other granulomatous or neoplastic diseases. Tuberculosis is the most common suspected diagnosis before confirmation of sporotrichosis. The chest radiograph most commonly demonstrates upperlobe cavitary disease with surrounding parenchymal infiltrates. The diagnosis can be suspected with high serologic titers or skin-test positivity, but needs to be confirmed by culture. The organism can usually be grown from sputum, as well as routine bronchoscopic procedures, open-lung biopsy specimens or pleural fluid. Histologic examination shows granulomas of both the caseating and noncaseating varieties. Frequently, organisms can be seen in necrotic areas of the lung tissue by diastase-modified GMS or PAS staining. Staining by direct fluorescent antibody technique can also be done and appears to be highly specific. Treatment is controversial, but total surgical resection of diseased lung as well as a perioperative regimen of SSKI or amphotericin B appears to be the most efficacious therapy. Medical therapy alone with SSKI or amphotericin B may be useful in selected cases but has been disappointing in the majority of reports. The imidazoles are usually ineffective, and the search for more effective medical therapy continues.