Thirty-four male Sprague-Dawley rats were divided into four groups: control animals and those receiving sodium nitroprusside (SNP), 2-chloroadenosine, or a high, inspired concentration of isoflurane to produce deliberate hypotension to a mean arterial blood pressure of 50 mmHg. Ventilation was controlled (FIO2= 0.3); control animals and those treated with sodium nitroprusside or 2-chloroadenosine breathed isoflurane 1.4 vol%, whereas isoflurane, 3.9 vol%, was required to produce hypotension by deep anesthesia alone. Multiple tissue oxygen tension values (PtO2) were measured at intervals of 10 μm over a distance of 2 mm by advancing an oxygen micro-electrode through the parietal cerebral cortex of all animals. The frequency of low tissue PO2values (<10 mmHg) was increased with all forms of deliberate hypotension, but the magnitude of this change (a shift to the left in the frequency histogram) was significantly different among techniques. The shift toward lower PtO2values during hypotension was least in animals receiving deep isoflurane anesthesia, intermediate in those receiving SNP, and greatest in those treated with 2-chloroadenosine. In rats, areas of the brain appear to be at risk for significant tissue hypoxia during hypotension produced by 2-chloroadenosine.