&NA;Acute hypertension disrupts the blood‐brain barrier and may neutralize the negative charge on cerebral endothelium. The goal of this study was to determine the effects of molecular charge on permeability of the blood‐brain barrier during acute hypertension. Intravital fluorescent microscopy and fluorescein‐labeled dextrans were used to evaluate disruption of the blood‐brain barrier during acute hypertension in rats. Disruption of the blood‐brain barrier was quantitated by calculating clearance of neutral dextran and of anionic dextran sulfate in two groups of rats. Pressure in pial venules, which are the primary site of disruption of the blood‐brain barrier during acute hypertension, was measured using a servo‐null device. When systemic arterial pressure was increased from 87±5 (mean±SEM) to 188±5 mm Hg, clearance of neutral dextran increased from 0.04±0.01 to 4.38±0.72 ml/sec×10−6. When systemic arterial pressure was increased from 91±4 to 181±3 mm Hg, clearance of anionic dextran sulfate increased from 0.02±0.01 to only 0.70±0.23 ml/sec × 10−6. Increases in pial venular pressure were similar in the two groups. Thus, similar increases in systemic arterial pressure and pial venular pressure during acute hypertension produce less disruption of the blood‐brain barrier to anionic dextran sulfate than neutral dextran. The findings suggest that 1) the net negative charge of cerebral vessels may be preserved during acute hypertension, and 2) molecular charge is an important determinant of the severity of disruption of the blood‐brain barrier during acute hypertension. (Circulation Research1989;64:658‐664)