To determine if topical dexamethasone administered to brain tumor beds would not only control peritumoral edema and suppress tumor growth but also prevent systemic steroid complications, we studied experimental brain tumors produced in 102 rabbits by implanted VX2 carcinoma cells. We separated 58 animals into three groups: 1) untreated rabbits (n = 15), 2) systemic dexamethasone-treated (4 mg/kg/day) rabbits (n = 18), and 3) topical dexamethasone-treated (2.5 microliters/h, osmotic pump) rabbits (n = 25). We administered systemic or topical dexamethasone from the third day or from the seventh day after tumor implantation, and sacrificed the animals on the 13th day. We compared survival in these three groups with that of another 44 rabbits, beginning treatment on the seventh day. We measured brain water content in the white matter of the sacrificed rabbits by the specific gravity method. We measured the length and width of the brain tumors of all the rabbits and estimated tumor volume. Systemic and topical dexamethasone administered from the third day produced statistically significant inhibition of tumor volume as well as a mean reduction in peritumoral brain edema in most tested sites. Systemic and topical dexamethasone treatment resulted in a statistically significant increase in survival relative to the untreated group. These results suggest that topical dexamethasone is efficacious in a brain tumor model and its administration to brain tumor beds constitutes a new therapeutic modality.