PURPOSE. To analyze the effect of different concentrations and application intervals of indocyanine green (ICG) on the retina in an experimental setting of macular surgery. METHODS. Twenty-one porcine eyes were used within 5 hours after enucleation. The eyes were hemisected and the vitreous removed. Different doses of ICG (up to 1 mg) were applied over the trephined macula, and the remainder of the eyecup was filled with a balanced salt solution (BSS). Both the ICG solution and the BSS were drained after 30 or 60 seconds and the complete eyecup irrigated and filled with fresh BSS. The posterior pole was then illuminated with a standard surgical light pipe and light source at maximum power for 3 minutes. Both the ICG-treated retina and the nontreated surrounding retina were processed for histology. RESULTS. Exposure of the retina at different concentrations of ICG either for 30 or 60 seconds, followed by illumination, caused no histologically detectable damage compared with the controls. No microarchitectural disorganization or cellular disruption was detected. The vitreoretinal interface seemed unaffected. CONCLUSIONS. Previously described severe damage to the inner retina of human donor eyes could not be found with even higher doses of ICG in this porcine model. Although differences within the species may contribute to these contradictory results, it is conceivable that the postmortem time and the vitality of the tissue influence the outcome in this ex vivo system.