High intensity focused ultrasound was employed to modify the permeability of the normal feline and canine blood-brain barrier (BBB) to a circulating vital dye--Evans blue (EB). The threshold doses (W sec/cm2) for focally increasing the permeability of the BBB in white matter (WM) and gray matter (GM) were as follows: internal capsule (WM)--340 to 680; thalamus (GM)--approximately 1326; and caudate nucleus (GM)--2284 to 2952. In the presence of supralesioning doses of ultrasound, the cross sectional area occupied by the EB was consistently greater than that of the attendant nonhemorrhagic lesion--thus suggesting that BBB changes may be inducible at sublesioning doses. These findings, in conjunction with those of others, suggest that high intensity focused ultrasound may have a role in the treatment of brain tumors based on cell destruction by two mechanisms: (a) direct, by the ultrasound and (b) indirect, by an antineoplastic agent which is delivered via an ultrasonically modified BBB.