PURPOSE. To characterize physiologic intereye differences (PIDs) in optic nerve head (ONH) architecture in six normal rhesus monkeys and compare them to intereye differences in three previously reported cynomolgus monkeys with early experimental glaucoma (EEG). METHODS. Trephinated ONH and peripapillary sclera from both eyes of six normal monkeys were serial sectioned, 3-D reconstructed, 3-D delineated, and parameterized. For each normal animal and each parameter, PID was calculated (both overall and regionally) by converting all left eye data to the right eye configuration and subtracting the right eye value from that of the left eye. Physiologic intereye percent difference (PIPD) was calculated as the PID divided by the measurement mean of the two eyes. For each EEG monkey, intereye (EEG minus normal) differences and percent differences for each parameter overall and regionally were compared to the PID and PIPD maximums. RESULTS. For all parameters the PID maximums were relatively small overall. Compared to overall PID maximums, overall intereye differences in EEG monkeys were greatest for laminar deformation and thickening, posterior scleral canal enlargement, cupping, and prelaminar neural tissue thickening. Compared with the regional PID maximums, the lamina cribrosa was posteriorly deformed centrally, inferiorly, inferonasally, and superiorly and was thickened centrally. The prelaminar neural tissues were thickened inferiorly, inferonasally, and superiorly. CONCLUSIONS. These data provide the first characterization of PID and PIPD maximums for ONH neural and connective tissue parameters in normal monkeys and serve to further clarify the location and character of early ONH change in experimental glaucoma. However, because of the species differences, the findings in EEG should be confirmed in EEG rhesus monkey eyes. © Association for Research in Vision and Ophthalmology.