A three-dimensional mathematical model was developed to examine the transient and steady state temperature distribution in the human brain during selective brain cooling (SBC) by unilateral intracarotid freezing-cold saline infusion. To determine the combined effect of hemodilution and hypothermia from the cold saline infusion, data was pooled together from studies investigating the effect of these two parameters on CBF and an analytical expression was derived describing the combined effect of the two factors. The Pennes bioheat equation was used to propagate the evolution of brain temperature using the thermal properties of the different cranial layers and the effect of cold saline infusion on CBF. Both a healthy brain and a brain with stroke (ischemic core and penumbra) were modeled. The core and the penumbra were simulated by reducing the CBF and metabolic rate. Simulations using different saline flow rates were performed. The results suggested that a flow rate of 30 ml/min is sufficient to induce moderate hypothermia within 10 minutes in the ipsilateral hemisphere. The brain with stroke cooled to lower temperatures than the healthy brain, mainly because the stroke itself limited the total intracarotid blood flow. Gray matter cooled twice as fast as white matter. The continuously falling hematocrit was the main time-limiting factor, limiting the SBC to a maximum of 3 hours. The study demonstrated that SBC using intracarotid saline infusion is feasible in humans and may be the fastest method of hypothermia induction.