BACKGROUND The response of cerebral blood flow to hypoxic hypoxia is usually effected by dilation of cerebral arterioles. However, the resulting changes in cerebral blood volume (CBV) have received little attention. We have determined, using susceptibility contrast magnetic resonance imaging (MRI), changes in regional CBV induced by graded hypoxic hypoxia. METHODS Six anaesthetized rats were subjected to incremental reduction in the fraction of inspired oxygen: 0.35, 0.25, 0.15, and 0.12. At each episode, CBV was determined in five regions of each hemisphere after injection of a contrast agent: superficial and deep neocortex, striatum, corpus callosum and cerebellum. A control group (n = 6 rats) was studied with the same protocol without contrast agent, to determine blood oxygenation level dependent (BOLD) contribution to the MRI changes. RESULTS Each brain region exhibited a significant graded increase in CBV during the two hypoxic episodes: 10-27% of control values at 70% SaO2, and 26-38% at 55% SaO2. There was no difference between regions in their response to hypoxia. The mean CBV of all regions increased from 3.6 (SD 0.6) to 4.1 (0.6) ml (100 g)-1 and to 4.7 (0.7) ml (100 g)-1 during the two hypoxic episodes, respectively (Scheffé F-test; P < 0.01). Over this range, CBV was inversely proportional to SaO2 (r2 = 0.80). In the absence of the contrast agent, changes due to the BOLD effect were negligible. CONCLUSIONS These findings imply that hypoxic hypoxia significantly raises CBV in different brain areas, in proportion to the severity of the insult. These results support the notion that the vasodilatory effect of hypoxia is deleterious in patients with reduced intracranial compliance.