Background: Hypoxic-ischemic encephalopathy (HIE) is responsible for a portion of the static motor encephalopathies of childhood. We have shown that experimental HI in rats at the age of 1 week can induce alteration in dopamine D2 receptors (Eur J Nuc Med.21:487-489). Aims:1)to assess the availability of D2 receptors in human neonates, 2)to investigate the effects of HI on D2 receptors in asphyxiated term infants. Methods: Six term infants (39/40wkGA)with birth asphyxia [mild HIE(Sarnat 1):n=3; moderate HIE,with seizures, (Sarnat 2): n=3] were investigated at the age of 10days. SPECT studies were performed one hour after an intraveinous injection of 37 MBq of 123-IBZM using a Ceraspect rotating camera over 30 minutes.An oral dose of potassium perchlorate (100mg) was given to each infant 2 hrs prior to the study to block the thyroid uptake of the tracer.On the same day, MR images of the brain were acquired to allow a correct assignement of the sites of 123-IBZM uptake. Results:No changes in vital signs were noted during or after the study. In all cases, SPECT images clearly demontrated that 123-IBZM was concentrated in the basal ganglia in agreement with a perfect delineation of these strutures using MRI. In infants with mild HIE(n=3)and normal MRimages the fixation of IBZM on D2 receptors was symmetrical and no uptake was noted in the other brain structures. Striatum/cerebellum ratio(S/C) was between 2.4 and 3.1.In 2 infants with moderate HIE a unilateral decrease in IBZM uptake was noted, despite no evidence of basal ganglia lesions at MRI.(S/C:1 and 1.5 vs 2.8and 3.2).In one infant with extended cerebral lesions a diffuse decrease in IBZM uptake was noted (S/C:1 and 1.3for right and left thalamus)Conclusion:these preliminary results indicate that 1) striatal dopamine D2 receptors are mature and biochemically active in the neonatal period; 2) Reduced D2 receptor activation may underlie extrapyramidal motor dysfunction that appears as a consequence of perinatal asphyxia.