We report the first study of laser-tissue interaction in the femtosecond time regime. Retinal damage thresholds and mechanisms produced by exposure to high-intensity femtosecond laser pulses were investigated in chinchilla grey rabbits. Exposures were performed using single laser pulses of 80 fs duration at 625 nm. ED50injury thresholds of 0.75 and 4.5 μJ were measured using fluorescein angiographic and ophthalmoscopic visibility criteria evaluating 204 laser exposures. Ultrastructural studies including light and electron microscopy were performed on selected lesions. Results suggest that the primary energy deposition in the retina occurs in melanin, However, in contrast to laser injuries produced by longer pulses, exposures of more than 100 × threshold in the50-100 muJ range did not produce significantly more severe lesions or hemorrhage. This suggests the presence of a nonlinear damage limiting mechanics in tissue exposed to femtosecond laser pulses.