The goal of the present study was to determine the effects of hypoxia and ischemia and the role of dopamine on phosphorylation of cAMP response element binding protein (CREB) in striatum of newborn piglets. Piglets, with and without prior injection of α-methyl-p-tyrosine (AMT), an inhibitor of dopamine (DA) synthesis, were subjected to 1 h of hypoxia (decreased inspired oxygen pressure, FiO 2 , from 21 to 6%) or 1 h of ischemia (ligation of both carotid arteries and hemorrhage to reduce the systemic arterial pressure to about 40 mm Hg), followed by 2 h recovery. Microvascular oxygen pressure in the cortex (pCO 2 ) was measured by quenching of phosphorescence. Extracellular DA was determined by in vivo microdialysis. Striatal levels of phosphorylated CREB (pCREB) and total CREB were determined by Western blots. In sham-operated animals, pCO 2 was 49.7 ± 8.2 mm Hg. During hypoxia and ischemia, pCO 2 decreased to 6.3 ± 1.8 mm Hg and 10.2 ± 2.7 mm Hg, respectively. There was statistical difference in the level of extracellular DA during hypoxia versus ischemia. At the end of ischemia and hypoxia, the levels of DA were 96 × 10 3 ± 24 × 10 3 % and 26 × 10 3 ± 12 × 10 3 % of control, respectively. The pCREB measured after 2 h recovery was not changed after hypoxia but was decreased to 47.8 ± 24% of control after ischemia. Depletion of endogenous DA abolished the ischemia-induced decrease in pCREB level. Total CREB did not change after either condition. It can be concluded that observed decreases of CREB phosphorylation following ischemia can be at least partially due to the high extracellular DA level.