Hypercapnia primarily affects cerebral blood flow (CBF) and not cerebral metabolism. We compared the CBF responses due to electrical forepaw stimulation before and after brief hypercapnia in male, non-ovarectomized female, and ovarectomized female rats. Prior to hypercapnia the CBF responses were similar for all three groups. Seven minutes after brief hypercapnic exposure the CBF responses to forepaw stimulation were augmented in all groups. However, both 30 and 60 min after hypercapnia, the magnitude of the CBF responses to forepaw stimulation remained elevated for males and ovarectomized females, but not for non-ovarectomized females. These results suggest that estrogen may modulate the upregulation of the CBF response observed after transient hypercapnia.