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Seven cases of infection due to Nocardia brasiliensis were identified over a 13-year period at Duke University Medical Center, Durham, North Carolina. These seven cases and a review of 55 cases in the literature reported from the United States show that N. brasiliensis can cause a wide spectrum of disease. Forty-six of the 62 patients had disease of skin and soft tissues. Cutaneous manifestations included cellulitis, pustules, ulcerations, pyoderma, subcutaneous abscesses, a lymphocutaneous syndrome, and mycetoma. Six patients had pleuropulmonary disease, and one patient had isolated central nervous system (CNS) involvement. Dissemination of disease, a characteristic generally attributed to Nocardia asteroides infection, was seen in eight instances. Patient ages ranged from one to 79 years; 51 of the patients were males. N. brasiliensis was an opportunistic pathogen in only 28% of the cases for which adequate clinical information was available, although trauma was an important predisposing feature of cutaneous disease (19 of 43 cases). Infection may be acquired either by cutaneous inoculation or respiratory inhalation. Clinical outcome is related to the site and extent of disease and to the presence or absence of serious underlying disease. All patients with skin and soft-tissue infections recovered, as did 83% of those with pulmonary involvement. For patients with disseminated or CNS disease, however, mortality was 67%. Traditional therapy with sulfonamides is not optimal for metastatic nocardial disease, and administration of trimethoprim-sulfamethoxazole may increase rates of cure.