We previously reported differential alterations of the mu, delta, and kappa opioid receptors following permanent middle cerebral artery occlusion. The present work studied the evolution of opioid receptor types following transient focal cerebral ischemia (tMCAO), as well as the putative predictive potential of early neurochemical alterations on the delayed ischemic damage. delta receptors were significantly decreased as early as 6 h post tMCAO (-22% approximately -57% vs. sham group), followed by a decrease in the mu binding site density at 24 h post tMCAO (-18% approximately -65%), in infarcted and penumbral cortices. Finally, early decreases in cortical opioid mu and delta receptor densities were found to significantly correlate (P < 0.001, r(2) = 0.48 and 0.75, respectively) with the occurrence of delayed histological damage. The high correlation between decreases in mu and delta receptor densities at 6 h post tMCAO and the histological damage that occurred at 24 h post tMCAO suggests that these early neurochemical alterations could be used as predictive markers of delayed ischemic damage.