The effects of picosecond laser-induced optical breakdown on tissue were investigated using high-intensity 40 ps Nd:YAG laser pulses at 1.06 microns. Tissue damage was evaluated using the corneal endothelium in vitro as a model system. Systematic studies were performed to determine the scaling of the tissue damage and damage range with pulse energy. For suprathreshold lesions, the radius of the damage zone varies as the cube root of the pulse energy, in agreement with simple physical scaling laws. A minimum damage range of less than 100 microns was observed for pulse energies of 8 muJ. Damage morphology was investigated by scanning electron microscopy. Three different damage patterns were observed; cell damage, cell removal, and rupture of Descemet's membrane. Different irradiation geometries were used to study damage mediated by either the shock wave or the cavitation bubble. Comparative studies using 10 ns pulses demonstrated that picosecond pulses yielded a significant reduction in collateral tissue damage.