The cerebral extraction and retention of three radioiodinated SPECT perfusion tracers were measured using residue detection in a baboon. A permeability-surface area product PS′ with special relevance to SPECT was calculated from the retention of tracer in the brain after 10 min. PS′ differs from the traditional PS value, which is calculated from the tracer clearance curve at 2 min. The PS′ values ranged from 50 to 95 mL/min/100 g, decreased in the order [123I]IMP > [123I]iodoperidol ≈ [123I]HIPDM, and did not differ for specific activities of 10 MBq/mmol to 74 TBq/mmol. These radioiodinated compounds exhibited extraction characteristics superior to those of [99mTc]HMPAO but underestimated cerebral blood flow when flows were above 20-30 mL/min/100 g, underscoring the need for development of a more ideal SPECT perfusion tracer.