BACKGROUND Although the development of significant interhemispheric intracranial pressure (ICP) gradients in the setting of unilateral stroke remains controversial, no study to date has investigated the existence of these gradients in a controlled, reproducible, clinically relevant model. Therefore, we used a primate model of reperfused hemispheric stroke to better characterize the development of these gradients. METHODS Bilateral intraparenchymal ICP was continuously monitored in 7 adult male baboons subjected to left hemisphere reperfused stroke. Interhemispheric ICP gradients were calculated for each baboon and plotted over time. Infarct volume was determined using T2-weighted magnetic resonance imaging (MRI) at sacrifice. RESULTS A bimodal distribution of interhemispheric ICP gradients was observed in animals with >20% infarct volume (22.1% +/- 0.9; range 21-23%) versus < or = 15% infarct volume (6.6% +/- 2.7; range 1-15%). In animals with >20% infarct volume, interhemispheric gradients developed early and persisted throughout the monitoring period. At 12 hours postreperfusion, animals with large infarcts demonstrated a mean pressure gradient of 13.8 +/- 4.3 mm Hg, compared to a mean gradient of -2.6 +/- 1.1 mm Hg for animals with < or =15% infarct volume. The difference in pressure gradients was statistically significant at all time points from 4 to 12 hours postreperfusion (p < 0.01). CONCLUSIONS These data suggest that, in nonhuman primates, infarcts of a size approaching 20% of the hemisphere may be associated with significant ICP gradients. With these larger infarcts, ipsilateral monitoring is required if regional cerebral perfusion pressure is to be accurately assessed.