Time-dependent variations in the brain temperature (Tt) are likely to be caused by fluctuations of cerebral blood flow (CBF) and cerebral metabolic rate of oxidative consumption (CMRO2) both of which are seemingly coupled to alterations in neuronal activity. We combined magnetic resonance, optical imaging, temperature sensing, and electrophysiologic methods in alpha-chloralose anesthetized rats to obtain multimodal measurements during forepaw stimulation. Localized changes in neuronal activity were colocalized with regional increases in Tt (by approximately 0.2%), CBF (by approximately 95%), and CMRO2 (by approximately 73%). The time-to-peak for Tt (42+/-11 secs) was significantly longer than those for CBF and CMRO2 (5+/-2 and 18+/-4 secs, respectively) with a 2-min stimulation. Net heat in the region of interest (ROI) was modeled as being dependent on the sum of heats attributed to changes in CMRO2 (Qm) and CBF (Qf) as well as conductive heat loss from the ROI to neighboring regions (Qc) and to the environment (Qe). Although tissue cooling because of Qf and Qc can occur and are enhanced during activation, the net increase in Tt corresponded to a large rise in Qm, whereas effects of Qe can be ignored. The results show that Tt increases slowly (by approximately 0.1 degrees C) during physiologic stimulation in alpha-chloralose anesthetized rats. Because the potential cooling effect of CBF depends on the temperature of blood entering the brain, Tt is mainly affected by CMRO2 during functional challenges. Implications of these findings for functional studies in awake humans and temperature regulation are discussed.