Ketoconazole was given orally to 33 patients with paracoccidioidomycosis and 23 with histoplasmosis. There were 55 men and one woman, and ages ranged from 28 to 67 years. Each patient had either the chronic disseminated or the chronic pulmonary form of disease. The diagnosis was established in 54 patients by culture of Paracoccidioides brasiliensis or Histoplasma capsulatum from lesions and in two patients by the clinical picture and results of serologic tests for histoplasmosis. The initial dosage was 400 mg per day. The dosage was reduced to 200 mg when a cure was achieved. The duration of treatment ranged from two to 18 months. Results of treatment were classified as very good (clinical and serologic cure) in 23 (41%) of the patients; good (clinical cure only) in 28 (50%); fair (partial improvement) in one (2%); and poor (no improvement) in three (5%). The results were not assessable in one patient who did not complete therapy. The three patients who did not respond to treatment had ⩽0.19 µg of ketoconazole/ml in their blood. The drug was well tolerated, and no side effects were reported.