Pulmonary mycoses can be life threatening in patients who are in an immunocompromised state stemming from defective host defenses or the use of certain treatment regimens. In 36 immunosuppressed patients undergoing thoracotomy for the treatment of pulmonary fungal disease, the underlying cause of immunosuppression was malignancy (n = 9), Wegener's granulomatosis (n = 4), hematologic disorders (aplastic anemia, 5-Q minus syndrome, or myelofibrosis) (n = 6), or chronic granulomatous disease of childhood (n = 17). The mean age of the patients was 25 years, and 89% were symptomatic (fever, n = 27; cough, n = 20; chest pain, n = 14; and other, n = 13). Chest x-ray studies revealed the presence of cavitary disease (n = 7), a mass (n = 8), infiltrates (n = 20), or cavity and infiltrate (n = 1). A preoperative diagnosis was lacking in 23 of the 36 patients. Procedures included wedge biopsy (n = 13), segmentectomy with or without wedge or chest wall resection (n = 5), lobectomy with or without chest wall resection (n = 16), wedge resection plus completion pneumonectomy (n = 1), and segmentectomy plus completion pneumonectomy (n = 1). Fungi identified included Aspergillus (n = 23), Zygomycetes (n = 4), Cryptococcus (n = 3), and other (n = 6; 1 each), and specific antifungal treatment was instituted in 34 of the patients (94%). The 31% operative (ie, < 30-day or inhospital) mortality was chiefly due to multiorgan system failure ( 9 11). Univariate analysis identified the following as prognostic of death during hospitalization: underlying hematologic disease (p2 = 0.012), angioinvasive disease (p2 = 0.0064), treatment with chemotherapy and steroids (p2 = 0.052), and a granulocyte percentage of 30% or less or a granulocyte count of 100 or less (p2 = 0.048). Moreover, multivariate analysis revealed that angioinvasion correlated with all risk factors and operative mortality. Nineteen patients are still alive at a mean follow-up period of 2.8 years. These data reinforce the risk of operation for the treatment or diagnosis of angioinvasive fungal disease in selected groups of immunosuppressed patients, and the need for improved pharmacologic agents in these high-risk populations.