Brain abscess caused by Pseudallescheria boydii is a highly lethal infection, usually seen in immunosuppressed patients. Five patients with P. boydii brain abscesses are described. Four of these patients acquired their infection after near-drowning; 1 patient developed an abscess after penetrating head trauma. Two patients survived their infections, which included involvement of other body sites (lung, eye, bone) as well as multiple undrained brain abscesses, after prolonged courses of high-dose parenteral miconazole (80-90 mg/kg/d). Progressive increases in miconazole dosage during the treatment periods were required to produce serum levels above the minimum inhibitory concentrations of the fungal isolates.